Geometric Mean Antibody Titers Research Articles

Safety, immunogenicity, and protective effective of inhaled COVID-19 vaccines: A systematic review and meta-analysis.

This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta-analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb-GMT) with aerosolised Ad5-nCoV (AAd5-nCoV) were all higher than those with inactivated vaccine (INA-nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96-2.69) and intramuscular Ad5-nCoV (IMAd5-nCoV) (SMD = 0.31; 95% CI: 0.14-0.48) against the original strain of SARS-CoV-2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5-nCoV compared to INA-nCoV or IMAd5-nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5-nCoV had a high immune response (including mucosal immunity) and provided protection against COVID-19 caused by the SARS-CoV-2 omicron variant. Further studies are needed to investigate the long-term safety of intranasal vaccine booster protection and various types of ICVs.

Human Cytomegalovirus Seropositivity and Its Influence on Oral Rotavirus Vaccine Immunogenicity: A Specific Concern for HIV-Exposed-Uninfected Infants.

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is aquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titres between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus specific antibody titres at 12 months (geometric mean ratio 1.01, 95%CI: 0.70,1.45; p=0.976) or fold-increase in RV-IgA titre between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66,1.52; p=0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titres at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95%CI: 0.17, 0.77; p=0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.

Comparable safety and non-inferior immunogenicity of the SARS-CoV-2 mRNA vaccine candidate PTX-COVID19-B and BNT162b2 in a phase 2 randomized, observer-blinded study

In the aftermath of the COVID-19 pandemic, the evolution of the SARS-CoV-2 into a seasonal pathogen along with the emergence of new variants, underscores the need for dynamic and adaptable responses, emphasizing the importance of sustained vaccination strategies. This observer-blind, double-dummy, randomized immunobridging phase 2 study (NCT05175742) aimed to compare the immunogenicity induced by two doses of 40 μg PTX-COVID19-B vaccine candidate administered 28 days apart, with the response induced by two doses of 30 µg Pfizer-BioNTech COVID-19 vaccine (BNT162b2), administered 21 days apart, in Nucleocapsid-protein seronegative adults 18–64 years of age. Both vaccines were administrated via intramuscular injection in the deltoid muscle. Two weeks after the second dose, the neutralizing antibody (NAb) geometric mean titer ratio and seroconversion rate met the non-inferiority criteria, successfully achieving the primary immunogenicity endpoints of the study. PTX-COVID19-B demonstrated similar safety and tolerability profile to BNT162b2 vaccine. The lowest NAb response was observed in subjects with low-to-undetectable NAb at baseline or no reported breakthrough infection. Conversely, participants who experienced breakthrough infections during the study exhibited higher NAb titers. This study also shows induction of cell-mediated immune (CMI) responses by PTX-COVID19-B. In conclusion, the vaccine candidate PTX-COVID19-B demonstrated favourable safety profile along with immunogenicity similar to the active comparator BNT162b2 vaccine.

Study on immune persistence of the CTN-1V strain rabies vaccine in humans

This study is a single-arm, single-center phase IV clinical trial on a rabies vaccine that has been marketed in China. The Vero cells and CTN-1V strain are used in the rabies vaccine product. The purpose of this study was to investigate the safety, immunogenicity and immune persistence of this product. One hundred and forty-nine participants were enrolled to the study, all of whom were included in the safety analysis set (SS), among which 116 participants were included in the protocol analysis set (PPS), One hundred and fifteen participants were included in the 6-month immune persistence analysis set (IPS6) and 111 in the 12-month immune persistence analysis set IPS12. Results showed that: 1) In the SS analysis set, adverse reactions were mainly pyrexia and pain at the vaccination site, the severity of which were mostly grade 1, and concentrated in 0–3 days after vaccination. No grade 3 or above adverse events and serious adverse events (SAE) related to the experimental vaccine were observed. 2) In the PPS analysis set, the antibody positive conversion rate reached 100% at 14 days after full immunization of the pre-immunized negative population; The antibody geometric mean titer (GMT) (95% CI) was 14.82 (13.00, 16.90). 3) The positive rate of serum neutralizing antibody was 93.91 % and the GMT at 1.58 IU/ml at 6 months after full immunization. The positive rate of neutralizing antibody was 85.59 % and GMT at 1.30 IU/ml at 12 months after immunization. Our results show that the human rabies vaccine with the CTN-1V strain and Vero cells as matrix had good safety, immunogenicity and immune persistence in our study.

Immunogenicity and safety of a bivalent (omicron BA.5 plus ancestral) SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose: interim analysis of a phase 3, non-inferiority, randomised, clinical trial

SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine. This interim analysis reports on day 28 immunogenicity and safety outcomes after one booster dose. In this phase 3, randomised, observer-blinded study conducted at 35 sites in Australia, medically stable, previously COVID-19-vaccinated (mRNA-based; ≥three doses) adults aged 18 years or older were enrolled and randomly allocated (1:1:1; via an interactive web response system) to receive two doses of bivalent (NVX-CoV2373 + NVX-CoV2540; bivalent group), authorised prototype (NVX-CoV2373; prototype group), or BA.5 (NVX-CoV2540; BA.5 group) vaccine. Only blinded personnel performed study assessments or had participant contact to collect data after study vaccination. Participants received vaccines containing 5 μg SARS-CoV-2 recombinant spike protein and 50 μg Matrix-M adjuvant, administered via a 0·5 mL intramuscular injection (2·5 μg of NVX-CoV2373 plus 2·5 μg of NVX-CoV2540 for the bivalent vaccine, prepared on-site as a 1:1 mixture). The coprimary endpoints include day 28 neutralising antibody geometric mean titre (GMT) ratios (GMTRs) to omicron BA.5 and the ancestral strain, and seroresponse rates to BA.5, in the bivalent and prototype groups. These endpoints were calculated in the per-protocol analysis set, which was defined as participants who had received a vaccine dose, had baseline and day 28 immunogenicity data, and were PCR-negative for SARS-CoV-2, with no major protocol deviations. The primary objective was to determine the primary outcome (antibody responses), which consisted of three comparisons: superiority of the bivalent versus prototype vaccine for neutralising antibody GMT to BA.5 (ie, lower bound of the GMTR 95% CI >1·0); non-inferiority of neutralising antibody seroresponse rate to BA.5 (ie, lower bound of the seroresponse rate 95% CI >-5%); and non-inferiority of neutralising antibody GMT to the ancestral strain (ie, lower bound of GMTR 95% CI >0·67). This trial was registered at ClinicalTrials.gov, number NCT05372588. Between March 22, 2023 and May 2, 2023, 837 participants were screened for eligibility and 766 were randomly allocated to receive the BA.5 (n=255), prototype (n=252), or bivalent (n=259) vaccine. After accounting for exclusions due to participants being baseline SARS-CoV-2-positive, having previous infection, or protocol deviations, the per-protocol analysis set included 694 participants (236 in BA.5 group, 227 in prototype group, and 231 in bivalent group). In this interim analysis (maximum follow-up 35 days after the first dose), the bivalent group, compared with the prototype group, had superior neutralising antibody responses to BA.5 (GMT 1017·8 [95% CI 891·0-1162·6] vs 515·1 [450·4-589·0]; GMTR 2·0 [1·69-2·33]) and a non-inferior seroresponse rate to BA.5 at day 28 (39·8% [33·5-46·5] vs 12·3% [8·4-17·3]; difference 27·5% [19·8-35·0]). The bivalent group also had non-inferior neutralising antibody responses to the ancestral strain (GMTR 1·0 [0·84-1·20]), compared with the prototype group. All vaccines were similarly well tolerated. All three coprimary endpoints were met in part 2 of the ongoing 2019nCoV-311 study. These data support the development of monovalent and/or bivalent vaccines for the most currently circulating variants, to optimise protection. With no new safety findings, further investigation of omicron-based subvariant vaccines is supported by the evidence. Novavax.

Persistence of Anti-SE36 Antibodies Induced by the Malaria Vaccine Candidate BK-SE36/CpG in 5-10-Year-Old Burkinabe Children Naturally Exposed to Malaria.

Information on the dynamics and decline/persistence of antibody titres is important in vaccine development. A recent vaccine trial in malaria-exposed, healthy African adults and children living in a malaria hyperendemic and seasonal area (Ouagadougou, Burkina Faso) was the first study in which BK-SE36/CpG was administered to different age groups. In 5- to 10-year-old children, the risk of malaria infection was markedly lower in the BK-SE36/CpG arm compared to the control arm. We report here data on antibody titres measured in this age-group after the high malaria transmission season of 2021 (three years after the first vaccine dose was administered). At Year 3, 83% of children had detectable anti-SE36 total IgG antibodies. Geometric mean antibody titres and the proportion of children with detectable anti-SE36 antibodies were markedly higher in the BK-SE36/CpG arm than the control (rabies) arm. The information obtained in this study will guide investigators on future vaccine/booster schedules for this promising blood-stage malaria vaccine candidate.

Safety and antibody response of the BNT162b2 SARS-CoV-2 vaccine in children aged 5–11 years with underlying diseases: A prospective observational study

BackgroundData on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5–11 years with underlying diseases are limited. Thus, our study aimed to address this gap. MethodsThis prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5–11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients’ electronic medical records. ResultsAmong 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199–1862] vs. 472 U/mL [200−1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847–11482] U/mL vs. 1127 [855–1486] U/mL, p < 0.001). ConclusionsBNT162b2 is acceptably safe and immunogenic for children aged 5–11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients.

Impact of dextran sulphate adjuentated S. aureus vaccine against the control of mastitis in lactating dairy buffaloes in Pakistan

The present study was conducted to evaluate two S. aureus vaccines in 100 mastitis free lactating buffaloes, dividing into 2 equal groups (B1, B2). The animals of B1 and B2 were administered with 2 shots of live attenuated and Dextran sulphate adjuvanted S. aureus vaccine at 15 days sequentially. The evaluation was done with different parameters i.e., serum and whey antibody titers, somatic cell count, milk fat %, milk protein, milk yield, vaccine efficacy, cost-benefit analysis, and colony count. There was a peak of geometric mean antibody titer 291 and 58 in LSAV while its climax 363 and 90 in DSAV at 2 and 6 months of study. In whey this level almost remained the same in both groups. In B1 and B2, somatic cell count kept on decreasing from day zero to the end of study. There was a non-significant difference in milk yield and fat percentage between the 2 groups. Milk protein concentration was significantly different between these groups and was better in B1 than B2. The surf field mastitis test-based quarter point prevalence decreased at 180 days in LASV and DSAV. In California mastitis test based, a significant decreased value was shown in both groups. Pre-vaccination and post-vaccination colony count of S. aureus was more in LSAV than in DSAV. Moreover, the preventative efficacy and cost benefit ratio of DSAV was more excellent as compared to LSAV.

Safety and immunogenicity of an indigenously developed tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap) in adults, adolescents, and children in India

ABSTRACTBackgroundThis study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)’s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap).Research Design and MethodsIn this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4–65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment.ResultsNo significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination.ConclusionsBooster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial

Licensed mRNA COVID-19 vaccines require booster doses to sustain SARS-CoV-2-specific responses, creating the need for novel, broadly immunogenic vaccines. We aimed to compare the immunogenicity, safety, and tolerability of ARCT-154-a self-amplifying mRNA vaccine against SARS-CoV-2 D614G variant-with the BNT162b2 (Comirnaty; Pfizer-BioNTech) mRNA vaccine when administered as a fourth-dose booster. This double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial, conducted at 11 outpatient clinical sites in Japan, enrolled healthy adults aged at least 18 years who had previously been immunised with two doses of an mRNA COVID-19 vaccine (BNT162b2 or mRNA-1273 [Spikevax; Moderna]) followed by a third dose of BNT162b2 at least 3 months before enrolment. Participants were randomly assigned, in a 1:1 ratio using an Interactive Response Technology system with a block size of four, and with stratification by age (18-64 years or ≥65 years) and by interval since last COVID-19 vaccination (<5 months or ≥5 months), to receive either ARCT-154 or BNT162b2 as a fourth-dose booster via deltoid intramuscular injection. Participants and investigators assessing outcomes were masked to group assignment. The primary objective, measured in per-protocol set 1 (consisting of participants with no evidence of previous SARS-CoV-2 infection who received their intended injection according to protocol), was to show that the immune response 28 days after the ARCT-154 vaccine was non-inferior to that of the BNT162b2 vaccine, measured in terms of both pseudovirus neutralising antibody geometric mean titre (GMT) ratios and seroresponse rates against the wild-type Wuhan-Hu-1 strain of SARS-CoV-2. Non-inferiority was declared when the lower limit of the 95% CI of the ARCT-154 to BNT162b2 GMT ratio exceeded 0·67, and when the lower limit for the difference in seroresponse rates exceeded -10%. Key secondary endpoints included the immune response against the omicron BA.4/5 subvariant, which was assessed for non-inferiority and superiority in per-protocol set 1. Safety was assessed in the full analysis set. This study was registered on the Japan Registry for Clinical Trials, jRCT 2071220080, and is ongoing. Between Dec 13, 2022, and Feb 25, 2023, we enrolled and randomly assigned 828 participants to receive ARCT-154 (n=420) or BNT162b2 (n=408) vaccines as a fourth-dose booster. In per-protocol set 1, the GMTs of surrogate neutralising antibodies induced against the Wuhan-Hu-1 SARS-CoV-2 strain in the ARCT-154 group (5641 [95% CI 4321-7363]) were non-inferior to those in the BNT162b2 group (3934 [2993-5169]) when measured at 28 days after boosting, with a GMT ratio of 1·43 (95% CI 1·26-1·63). Seroresponse rates were 65·2% (95% CI 60·2-69·9) in the ARCT-154 group versus 51·6% (46·4-56·8) in the BNT162b2 group, a difference of 13·6% (95% CI 6·8-20·5). GMTs against the omicron BA.4/5 variant on day 29 were 2551 (1687-3859) in the ARCT-154 group and 1958 (1281-2993) in the BNT162b2 group-a GMT ratio of 1·30 (1·07-1·58)-with seroresponse rates of 69·9% (65·0-74·4) and 58·0% (52·8-63·1). Both boosters were equally well tolerated. No treatment-related deaths were reported, nor were there severe or serious adverse events considered to be causally associated related to study vaccination. One serious adverse event, a foot deformity reported in a participant in the BNT162b2 group, was observed but determined not to have a causal relationship to the study vaccination. One severe adverse event, a case of abnormal hepatic function in the ARCT-154 group, was considered to be related to study vaccine. Adverse events of special interest for detection of myocarditis and pericarditis included chest pain (one case in the ARCT-154 group and three cases in the BNT162b2 group) and shortness of breath (two cases in the BNT162b2 group), all of which were considered to have a reasonable possibility of being related to vaccination. Local reactions were reported by 398 (95%) of 420 participants receiving the ARCT-154 vaccine and 395 (97%) of 408 participants receiving the BNT162b2 vaccine, and solicited systemic adverse events by 276 (66%) of those receiving the ARCT-154 vaccine and 255 (63%) of those receiving the BNT162b2 vaccine. Adverse events were mainly mild in severity, occurring and resolving within 3-4 days after vaccination. In adults who had previously received three doses of an mRNA COVID-19 vaccine, immune responses 28 days after an ARCT-154 booster dose were non-inferior to those observed after a BNT162b2 booster dose for the Wuhan-Hu-1 strain of SARS-CoV-2 and superior for the Omicron BA.4/5 variant. Increased immune responses at 28 days might provide increased likelihood of protection against these strains during this period and could also result in longer duration of protection. Further studies will assess the immunogenicity induced against more recent SARS-CoV-2 variants. Japanese Ministry of Health, Labour, and Welfare. For the Japanese translation of the abstract see Supplementary Materials section.

Evaluation of humoral immune responses of experimental animals to the recombinant SARS-CoV-2 spike ectodomain with the ISCOM adjuvant

Scientific relevance. The use of recombinant antigens in vaccine production is limited because vaccines based on such antigens tend to have low immunogenicity. However, a COVID-19 vaccine that combines recombinant SARS-CoV-2 spike glycoprotein as its antigen and virus-like immune-stimulating complexes (ISCOMs) as its adjuvant (Nuvaxovid) induces a protective virus-neutralising response. The State Research Center of Virology and Biotechnology “Vector” (hereinafter, Vector) has developed the ISCOM adjuvant Matrix-V, which plays a key role in inducing virus-neutralising antibodies. Studying Matrix-V will provide for the wide use of recombinant antigens combined with this adjuvant in the development and production of novel Russian vaccines.Aim. This study aimed to evaluate the humoral immune responses of experimental animals to intramuscular injections of a complex combining the recombinant Wuhan-type SARS-CoV-2 spike RBD antigen and the virus-like ISCOM adjuvant containing Quillaja saponaria saponins.Materials and methods. The Matrix-V ISCOM adjuvant was produced using Vector’s proprietary technology, which involves cross-flow filtration through Sartorius VivaFlow cassettes. To determine the saponin and residual detergent concentrations in Matrix-V, the authors conducted high-performance liquid chromatography. Having produced the recombinant SARS-CoV-2 RBD antigen, the authors used electron microscopy to analyse the ultrastructure of the ISCOM–antigen complex. In the study of the ISCOM–antigen complex, 25 female Balb/c mice (5 groups) and 15 male and female outbred guinea pigs (3 groups) received two intramuscular injections with a 14-day interval. Serum tests relied on virus neutralisation (VN) and enzyme-linked immunosorbent assay (ELISA) methods and used antigens of 8 SARS-CoV-2 variants (State Collection of Viruses and Rickettsia, Vector). The authors used Statistica 10 to analyse the results.Results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) alone did not induce statistically significant virus-neutralising antibody responses, as shown by the VN results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) adjuvanted with Matrix-V (25 μg) resulted in geometric mean antibody titres of 1:83–1:178 (mice) and 1:174–1:587 (guinea pigs) in the VN tests with the Wuhan variant. One injection of the antigen (1 μg or 7 μg) with Matrix-V (25 μg) induced antibodies only in individual cases, as demonstrated by the VN and/or ELISA results. The most intensive immune response was observed in ELISA tests with the Delta variant after two injections of the Ecto-S-Wuhan (1 μg) and Matrix-V (25 μg) complex. Immune responses did not differ between the group that received two injections of the Ecto-S-Wuhan antigen (1 μg) without the ISCOM adjuvant and the negative control group (titres below 1:100; p=0.95). Two injections of the SARS-CoV-2 RBD antigen (7 μg) without the ISCOM adjuvant induced antibodies in mice (titres between 1:248 and 1:1477).Conclusions. Two intramuscular injections of the complex containing the recombinant SARS-CoV-2 RBD antigen and the Matrix-V ISCOM adjuvant induce virus-neutralising antibodies. The approach proposed by the authors has the potential for use in the development of immunobiological medicinal products to prevent and treat a wide range of infectious diseases.

The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients.

COVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines; consequently, the eradication of SARS-CoV-2 is far from happening. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous conditions associated with worsening health and 34 (33%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger [42, interquartile range (IQR) = 17.5] than other hospitalized COVID-19 patients (59, IQR = 22, P < 0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% confidence interval: 344-990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression, but a high neutralizing response was associated with a shorter length of stay, suggesting the benefit of early-stage immunotherapy treatment of COVID-19. Nevertheless, these data highlight the importance of more Nab screening studies to predict faster recovery.IMPORTANCEThe study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.

The 6-Month Antibody Durability of Heterologous Convidecia Plus CoronaVac and Homologous CoronaVac Immunizations in People Aged 18-59 Years and over 60 Years Based on Two Randomized Controlled Trials in China.

Previous reports have shown that heterologous boosting with the AD5-vectored COVID-19 vaccine Convidecia based on a primary series of two doses of inactivated vaccine induces increasing immune responses. However, the immune persistence until 6 months after the heterologous prime-boost immunization was limited. Participants were from two single-center, randomized, controlled, observer-blinded trials, which involved individuals of 18-59 years of age and over 60 years of age. Eligible participants who previously primed with one dose or two doses of CoronaVac were stratified and randomly assigned to inoculate a booster dose of Convidecia or CoronaVac. Neutralizing antibodies against a live SARS-CoV-2 prototype virus and Delta and Omicron (B.1.1.529) variants, pseudovirus neutralizing antibodies against Omicron BA.4/5 variants, and anti-SARS-CoV-2 RBD antibodies at month 6 were detected, and the fold decreases and rate difference were calculated by comparing the levels of antibodies at month 6 with the peak levels at month 1. The neutralizing antibody titers against prototype SARS-CoV-2, RBD-specific IgG antibodies, and the Delta variant in the heterologous regimen of the CoronaVac plus Convidecia groups were significantly higher than those of the homologous prime-boost groups. In three-dose regimen groups, the geometric mean titers (GMTs) of neutralizing antibodies against prototype SARS-CoV-2 were 30.6 (95% CI: 25.1; 37.2) in the heterologous boosting group versus 6.9 (95% CI: 5.6; 8.6) in the homologous boosting group (p < 0.001) at month 6 in participants aged 18-59 years, and in the two-dose regimen, the neutralizing antibody GMTs were 8.5 (95% CI: 6.2; 11.7) and 2.7 (2.3 to 3.1) (heterologous regimen group versus CoronaVac regimen group, p < 0.001). Participants aged over 60 years had similar levels of neutralizing antibodies against the prototype, with GMTs of 49.1 (38.0 to 63.6) in the group receiving two doses of CoronaVac plus one dose of Convidecia versus 9.4 (7.7 to 11.4) in the group receiving three doses of CoronaVac (p < 0.001) and 11.6 (8.4 to 16.0) in the group receiving one dose of CoronaVac and one dose of Convidecia versus 3.3 (2.7 to 4.0) in the group receiving two doses of CoronaVac (p < 0.001). Compared with day 14, over sixfold decreases in neutralizing antibody GMTs were observed in the heterologous groups of the three- or two-dose regimen groups of younger and elderly participants, while in the homologous regimen groups, the GMTs of neutralizing antibodies decreased about fivefold in the two age groups. The heterologous prime-boost regimen with two doses of CoronaVac and one dose of Convidecia was persistently more immunogenic than the regimen of the homologous prime-boost with three doses of CoronaVac.

Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

Safety and immunogenicity of the COVID-19 mRNA vaccine CS-2034: A randomized, double-blind, dose-exploration, placebo-controlled multicenter Phase I clinical trial in healthy Chinese adults

The novel coronavirus pneumonia (COVID-19) is an infectious disease caused by the infection of a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths. We aimed to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034, CanSino, Shanghai, China) in adults without COVID-19 infection from China. This is a multicenter Phase I clinical trial with a randomized, double-blinded, dose-exploration, placebo-controlled design. The trial recruited 40 seronegative participants aged 18-59 years who had neither received any COVID-19 vaccine nor been infected before. They were divided into a low-dose group (administered with either the CS-2034 vaccine containing 30μg of mRNA or a placebo of 0.3ml type 5 adenovirus vector) and a high-dose group (administered with either the CS-2034 vaccine containing 50μg of mRNA or a placebo of 0.5ml type 5 adenovirus vector). Participants were randomly assigned in a 3:1 ratio to receive either the mRNA vaccine or a placebo on days 0 and 21 according to a two-dose immunization schedule. The first six participants in each dosage group were assigned as sentinel subjects. Participants were sequentially enrolled in a dose-escalation manner from low to high dose and from sentinel to non-sentinel subjects. Blood samples were collected from all participants on the day before the first dose (Day 0), the day before the second dose (day 21), 14 days after the second dose (day 35), and 28 days after the second dose (day 49) to evaluate the immunogenicity of the CS-2034 vaccine. Participants were monitored for safety throughout the 28-day follow-up period, including solicited adverse events, unsolicited adverse events, adverse events of special interest (AESI), and medically attended adverse events (MAE). This report focuses solely on the safety and immunogenicity analysis of adult participants aged 18-59 years, while the long-term phase of the study is still ongoing. This study is registered at ClinicalTrials.gov, NCT05373485. During the period from May 17, 2022, to August 8, 2022, a total of 155 participants aged 18-59 years were screened for this study. Among them, 115 participants failed the screening process, and 40 participants were randomly enrolled (15 in the low-dose group, 15 in the high-dose group, and 10 in the placebo group). Throughout the 28-day follow-up period, the overall incidence of adverse reactions (related to vaccine administration) in the low-dose group, high-dose group, and placebo group was 93.33% (14/15), 100.00% (15/15), and 80.00% (8/10), respectively. There was a statistically significant difference in the incidence of local adverse reactions (soreness, pruritus, swelling at the injection site) among the low-dose group, high-dose group, and placebo group (P=0.002). All adverse reactions were mainly of severity grade 1 (mild) or 2 (moderate), and no adverse events of severity grade 4 or higher occurred. Based on the analysis of Spike protein Receptor Binding Domain (S-RBD) IgG antibodies against the BA.1 strain, the seroconversion rates of antibodies at day 21 after the first dose were 86.67%, 93.33%, and 0.00% in the low-dose group, high-dose group, and placebo group, respectively. The geometric mean titer (GMT) of antibodies was 61.2(95%CI 35.3-106.2), 55.4(95%CI 36.3-84.4), and 15.0(95%CI 15.0-15.0), and the geometric mean fold increase (GMI) was 4.08(95%CI 2.35-7.08), 3.69(95%CI 2.42-5.63), and 1.00(95%CI 1.00-1.00) for each group. At day 28 after the full vaccination, the seroconversion rates of antibodies were 100.00%, 93.33%, and 0.00%, and the GMT of antibodies was 810.0(95%CI 511.4-1283.0), 832.2(95%CI 368.1-1881.6), and 15.0(95%CI 15.0-15.0), and the GMI was 54.00(95%CI 34.09-85.53), 55.48(95%CI 24.54-125.44), and 1.00(95%CI 1.00-1.00) for each group, respectively. Based on the analysis of CD3+/CD4+ cell cytokine response, the percentages of IL-2+, IL-4+, IFN-γ+, and TNF-α+ cells increased after 14 days and 28 days of full vaccination in both the low-dose group and high-dose group. The increase was most pronounced in the high-dose group. At day 28 after the full vaccination, both the low-dose and the high-dose CS-2034 vaccine were able to induce the production of high titers of S-RBD IgG antibodies against the BA.1 strain. Adverse reactions in the low-dose and high-dose groups were mainly of severity grade 1 or 2, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

Clinical trial of tolerability, safety, and immunogenicity of the Russian influenza inactivated split vaccine Flu-m in children from 6 months to 9 years of age

Purpose: To study the reactogenicity, safety and immunogenicity of the Russian vaccine Flu-M in comparison with Vaxigrip vaccine for influenza prevention in children aged from 6 months to 9 years (phase III).Materials and Methods. In 2021, a clinical study was conducted in which children aged 6 months to 9 years were immunized with Flu-M vaccine (produced by SPbSRIVS, Russia) and Vaxigrip vaccine (produced by Sanofi Pasteur S.A., France). After randomization one group of children was vaccinated with Flu-M, the other with Vaxigrip, and monitored for 180±3 days after vaccination. Children vaccinated between 3 and 9 years of age were studied in phase I, and between 6 months and 3 years of age in phase II. Tolerability and safety were assessed by the frequency and extent of adverse events, as well as by the assessment of vital signs and physical examination. Immunological efficacy assessment criteria were geometric mean antibody titer, seroconversion level, seroconversion factor, seroprotection level.Results. Both vaccines (Flu-M and Vaxigrip) were shown to be well tolerated by children of both age groups. No serious adverse events or severe adverse events were reported in the study. Immunological efficacy criteria were achieved for both vaccines for all strains of influenza virus in children of both age groups at 28 and 56 days after vaccination. No cases of influenza or acute respiratory infections were seen at 180±3 days postvaccination.Conclusion. The results of the clinical study show that the Flu-M and Vaxigrip vaccines are comparable in both age groups of children.The trial is registered at ClinicalTrials.gov (NCT 05470582).

Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China

ObjectivesDuring the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. MethodsThis study was a follow-up trial of the “Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial.” Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. ResultsThe geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. ConclusionCo-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Immunogenicity and safety of AZD2816, a beta (B.1.351) variant COVID-19 vaccine, and AZD1222 (ChAdOx1 nCoV-19) as third-dose boosters for previously vaccinated adults: a multicentre, randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study in the UK and Poland

This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters. This phase 2/3, partly double-blinded, randomised, active-controlled study was done at 19 sites in the UK and four in Poland. Adult participants who had received a two-dose AZD1222 or mRNA vaccine primary series were randomly assigned by means of an Interactive Response Technology-Randomisation and Trial Supply Management system (1:1 within each primary-series cohort, stratified by age, sex, and comorbidities) to receive AZD1222 or AZD2816 (intramuscular injection; 5 × 1010 viral particles). Participants, investigators, and all sponsor staff members involved in study conduct were masked to randomisation. AZD1222 and AZD2816 doses were prepared by unmasked study staff members. The primary objectives were to evaluate safety and humoral immunogenicity (non-inferiority of day-29 pseudovirus neutralising antibody geometric mean titre [GMT] against ancestral SARS-CoV-2: AZD1222 booster vs AZD1222 primary series [historical controls]; margin 0·67; SARS-CoV-2-seronegative participants). This study is registered with ClinicalTrials.gov, NCT04973449, and is completed. Between June 27 and Sept 30, 2021, 1394 participants of the 1741 screened were randomly assigned to AZD1222 or AZD2816 following an AZD1222 (n=373, n=377) or mRNA vaccine (n=322, n=322) primary series. In SARS-CoV-2-seronegative participants receiving AZD1222 or AZD2816, 78% and 80% (AZD1222 primary series) and 90% and 93%, respectively (mRNA vaccine primary series) reported solicited adverse events to the end of day 8; 2%, 2%, 1%, and 1% had serious adverse events and 12%, 12%, 10%, and 11% had adverse events of special interest, respectively, to the end of day 180. The primary immunogenicity non-inferiority endpoint was met: day-29 neutralising antibody GMT ratios (ancestral SARS-CoV-2) were 1·02 (95% CI 0·90-1·14) and 3·47 (3·09-3·89) with AZD1222 booster versus historical controls (AZD1222 and mRNA vaccine primary series, respectively). Responses against beta were greater with AZD2816 versus AZD1222 (GMT ratios, AZD1222, mRNA vaccine primary series 1·84 [1·63-2·08], 2·22 [1·99-2·47]). Both boosters were well tolerated, with immunogenicity against ancestral SARS-CoV-2 similar to AZD1222 primary-series vaccination. AZD2816 gave greater immune responses against beta versus AZD1222. AstraZeneca.

Quantitative analysis of protective T cell immunity against brucellosis

The results of study relationship between antigen reactivity of T-lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis are presented. Тaking into account the peculiarities of immunopathogenesis brucellosis and prevailing role of adaptive T-cell immunity to protect against the causative agent of infection, possibility predictive evaluation of protective immunity against brucellosis using CAST-tests is considered as the most important aspect of brucellosis problems. There is an obvious need for an ex vivo correlation analysis of the activity of antigen stimulation of T cells and the intensity of protective immunity formed after vaccination. A close direct proportional relationship was established between the number of live microbial cells Brucella abortus 19BA vaccine strain administered and increase in ex vivo CD3-cell activation. A close correlation was revealed between ex vivo value of antigen-induced stimulation CD3-lymphocytes and level of post-vaccination immunological protection against brucellosis infection. It has been shown that in biomodels vaccinated against brucellosis with a T-lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo expression CD25), 100% protection from the development of brucellosis infection after infection with Brucella melitensis at a dose of 1 × 103 live microbial cells are provided. At the same time, there was a lack of a close correlation between an increase in the dose of brucella vaccine strain administered to biomodels and a change in geometric mean antibody titer, presence of a weakly pronounced relationship between level of agglutinins and immunological protection of biomodels from development brucellosis infection and indicators bacterial contamination body.Based on results of study, it was demonstrated that it is possible to quantify the formation and protective activity of T-cell immunity to causative agent of brucellosis based on analysis of level antigen reactivity of CD3-lymphocytes ex vivo. The data obtained and described methodological approach can be used as a predictive criterion in assessing protective level of cellular immunity to causative agent of brucellosis in vaccinated or recovering patients, as well as in order to analyze effectiveness of specific prophylaxis brucellosis and study immunogenicity and protective properties candidate for brucellosis vWe present the results of studies related to antigen reactivity of T lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis. Due to peculiarities of immunopathogenesis in brucellosis infection and prevailing role of adaptive T cell immunity for protection against the causative agent of infection, a predictive evaluation of protective immunity against brucellosis using CAST-tests is considered the most important issue in the field. There is an obvious need for ex vivo analysis of correlations between the activity of antigen stimulation of T cells, and the intensity of protective immunity raised after vaccination. A close direct relationship was established between the number of live microbial cells of Brucella abortus 19BA vaccine strain administered, and increase in ex vivo CD3 cell activation. A close correlation (r = -0.841 ÷ -0.966, R2 = 0.708 ÷ 0.969) was revealed between ex vivo values of antigeninduced stimulation of CD3 lymphocytes, and the levels of post-vaccination immunological protection against brucellosis infection. We have shown that, in biomodels vaccinated against brucellosis with a T lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo CD25 expression), 100% protection against brucellosis infection was achieved after contamination with Brucella melitensis at a dose of 1×103 live microbial cells. At the same time, a lack of a close correlation was noted between an increased dose of Brucella vaccine strain administered to biomodels, and a change in geometric mean of antibody titer (R2 = 0.357÷0.404), along with a weak relationship between the levels of agglutinins and immunological protection of biomodels from developing brucellosis infection and indices of in vivo bacterial contamination.These results suggest an opportunity to quantify development and protective activity of T cell immunity to the causal agent of brucellosis based ex vivo levels of antigen reactivity of CD3 lymphocytes. A correlation analysis between the state of T cell antigen reactivity and immunological resistance to brucellosis infection indicated a high degree of closeness between these indices. The key influence on activity of protective immunity is exerted by the levels of antigen reactivity of T lymphocytes, whereas the quotient of antigenic stimulation in CD3+CD25+ population may be considered the most informative index of immune protective activity. The data obtained and the described methodology may be used as a predictive criterion in assessing protective level of cellular immunity to causative agent of brucellosis in vaccinated or recovering patients, testing the efficiency of specific prophylaxis in brucellosis and studying immunogenicity and protective properties of candidate vaccines against brucellosis.