Levels Of Neutralizing Antibodies Research Articles

Nasal and pharyngeal mucosal immunity to poliovirus in children following routine immunization with inactivated polio vaccine (IPV) in the United States of America.

Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review.

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.

Immunogenicity and safety of Ad26.RSV.preF/RSV preF protein vaccine at predicted intermediate- and end-of-shelf-life as an evaluation of potency throughout shelf life

ABSTRACT This study assessed three Ad26.RSV.preF/RSV preF protein combinations, combining different Ad26.RSV.preF doses and naturally aged preF protein, representing the expected critical vaccine quality attributes close to release, around intermediate shelf-life (ISL) and near-presumed end-of-shelf-life (EoSL), as a way to evaluate the vaccine immunogenicity and safety throughout its shelf-life. A single dose of Ad26.RSV.preF/RSV preF protein vaccine was administered to adults 60–75 years of age. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-day, 28-day, and 6-month periods after vaccination, respectively. RSV preF-binding antibody concentrations and RSV neutralizing titers were measured 14 days post-vaccination as primary and secondary endpoints, respectively; binding antibodies were also measured 6 months post-vaccination. The RSV preF-binding antibody responses induced by Ad26.RSV.preF/RSV preF protein vaccine lots representing the critical quality attributes around ISL and near presumed EoSL were noninferior to the responses induced by the vaccine lot representing the critical quality attributes near release. The RSV preF-binding and RSV neutralizing antibody levels measured 14 days post-vaccination were similar across the 3 groups. RSV preF-binding antibody concentrations were also similar 6 months post-vaccination. Solicited AEs were mostly mild to moderate in intensity, and a decreased reactogenicity was observed from the Release group to the ISL and EoSL group. None of the reported SAEs were considered related to study vaccination. The study provided evidence of sustained immunogenicity and safety over the intended shelf-life of the Ad26.RSV.pref/RSV preF protein vaccine. The three vaccine lots had acceptable safety profiles.

Coronavirus infection and neutralizing antibody responses among liver transplant recipients: single-center study

BackgroundLiver transplant (LT) recipients are classified as a high-risk group and should receive regular surveillance for COVID-19 and are expected to have higher viral load and prolonged viral shedding. Virus-specific neutralizing antibodies (NAb), induced by infection, can prevent viral infection by deactivating viral access to host receptors.AimTo estimate the incidence of SARS-CoV-2 infections and ascertain the levels of NAb among LT recipients.MethodThis cross-sectional study included LT recipients. The survey included 14 parameters about demography, date since operation, and immunosuppressant medications and 11 parameters about COVID-19 infection. NAb was done by electrochemiluminescence immunoassay.ResultsOnly 39 LT recipients responded to this survey. Their median age was 57, and 74.4% of them were men. Comorbidities were present in 64% of cases, and DM was the most common comorbidity. Immunosuppressants used were Tacrolimus in 56.4% and Tacrolimus with mycophenolate mofetil in 15.4%. Fifteen cases (38.5%) had suspected infection, and 2 (5.1%) had confirmed infection. Three patients (17.6%) were hospitalized with no mortality. NAb was done in 34 cases, and it was positive in 5 cases (14.7%) with a median level (range) of 0.075 (0.04–27). Three out of 5 cases with a positive NAb test did not give a history of either suspected or confirmed COVID-19 infection.ConclusionCOVID-19 surveillance in LT recipients is important and suggests a relatively favorable clinical course despite the presumed challenges of immunosuppression. COVID-19 was associated with low hospitalization in LT recipients. NAb indicates a potential immune response even in asymptomatic LT recipients.Trial registrationClinical Trial.gov NCT04565782. September 15 2022.

SARS-CoV-2 Neutralization Assays Used in Clinical Trials: A Narrative Review.

Since the emergence of COVID-19, extensive research efforts have been undertaken to accelerate the development of multiple types of vaccines to combat the pandemic. These include inactivated, recombinant subunit, viral vector, and nucleic acid vaccines. In the development of these diverse vaccines, appropriate methods to assess vaccine immunogenicity are essential in both preclinical and clinical studies. Among the biomarkers used in vaccine evaluation, the neutralizing antibody level serves as a pivotal indicator for assessing vaccine efficacy. Neutralizing antibody detection methods can mainly be classified into three types: the conventional virus neutralization test, pseudovirus neutralization test, and surrogate virus neutralization test. Importantly, standardization of these assays is critical for their application to yield results that are comparable across different laboratories. The development and use of international or regional standards would facilitate assay standardization and facilitate comparisons of the immune responses induced by different vaccines. In this comprehensive review, we discuss the principles, advantages, limitations, and application of different SARS-CoV-2 neutralization assays in vaccine clinical trials. This will provide guidance for the development and evaluation of COVID-19 vaccines.

Clinical manifestations and long-term symptoms associated with SARS-CoV-2 omicron infection in children aged 0–17 years in Beijing: a single-center study

ObjectiveThe study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0–17 years with the Omicron variant, and summarize the persistent symptoms or new-onset clinical manifestations from 4 to 12 weeks after acute COVID. Explore the association between the vaccination status and SARS-CoV-2 neutralizing antibody levels post infection among preschool-aged children. The comprehensive study systematically describes the clinical characteristics of children infected with SARS-CoV-2, providing a foundation for diagnosis and evaluating long-term COVID in pediatric populations.MethodsThe study enrolled children who were referred to the Children's Hospital, Capital Institute of Pediatrics, (Beijing, China) from January 10, 2023 to March 31, 2023. Participants were classified as infant and toddlers, preschool, school-age, and adolescent groups. Children or their legal guardians completed survey questionnaires to provide information of previous SARS-CoV-2 infection history, as well as clinical presentation during the acute phase and long-term symptoms from 4 to 12 weeks following infection. Furthermore, serum samples were collected from children with confirmed history of SARS-CoV-2 infection for serological testing of neutralizing antibodies.ResultsThe study recruited a total of 2,001 children aged 0–17 years who had previously tested positive for SARS-CoV-2 through nucleic acid or antigen testing. Fever emerged as the predominant clinical manifestation in 1,902 (95.1%) individuals with body temperature ranging from 37.3 to 40.0°C. Respiratory symptoms were identified as secondary clinical manifestations, with cough being the most common symptom in 777 (38.8%) children, followed by sore throat (22.1%), nasal congestion (17.8%), and runnning nose (17.2%). Fatigue (21.6%), headache (19.8%) and muscle-joint pain (13.5%) were frequently reported systemic symptoms in children. The proportion of children with symptoms of SARS-CoV-2 infection varied across age groups. 1,100 (55.0%) children experienced persistent symptoms from 4 to 12 weeks post the acute phase of infection. Trouble concentrating (22.1%), cough (22.1%), and fatigue (12.1%) were frequently reported across age groups in the extended period. A limited number of children exhibited cardiovascular symptoms with chest tightness, tachycardia, and chest pain reported by 3.5%, 2.5%, and 1.8% of children, respectively. Among 472 children aged 3–5 years, 208 children had received two doses of SARS-CoV-2 vaccine at least 6 months prior to infection, and no association was found between the incidence of long-term COVID and pre-infection vaccination statuses among the 3–5 years age groups (χ2 = 1.136, P = 0.286).ConclusionsIn children aged 0–17 years infected with SARS-CoV-2 Omicron variant, fever was the primary clinical manifestation in the acute phase, followed by respiratory symptoms, systemic non-specific and digestive presentations. In particular, respiratory and digestive system symptoms were more frequent in children aged above 6 years. Regarding the long-term symptoms from 4 to 12 weeks post-infection, the most common presentations were concentrating difficulty, cough, and fatigue. The incidence of persistent symptoms of SARS-CoV-2 did not exhibit a significant correlation with vaccination status, which was attributed to the waning efficacy of the vaccine-induced humoral immune response after 6 months.

Humoral Immunity across the SARS-CoV-2 Spike after Sputnik V (Gam-COVID-Vac) Vaccination.

SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies.

Longitudinal study of immunity to SARS-CoV2 in ocrelizumab-treated MS patients up to 2 years after COVID-19 vaccination.

(1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.

Third-generation smallpox vaccines induce low-level cross-protecting neutralizing antibodies against Monkeypox virus in laboratory workers

Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.

Humoral response superiority of the monovalent XBB.1.5 over the bivalent BA.1 and BA.5 mRNA COVID-19 vaccines

JN.1, the dominating SARS-CoV-2 variant, is antigenically distinct from ancestral BA.1, BA.5 and XBB.1.5 variants, raising concern about effectiveness of updated COVID-19 vaccines. Here, we compared the neutralizing antibody response against JN.1, 1-month after receipt of the three available Moderna mRNA vaccines. Sera obtained from 37, 30 and 30 XBB.1.5, BA.1 and BA.4-5 -vaccine recipients, respectively, were tested for anti-RBD IgG and for JN-1 specific neutralizing antibody levels. Geometric mean fold rise (GMFR) in JN.1 specific neutralizing titers was 27 (95 % CI: 17–43.1), 10.1 (95 % CI: 6.48–15.7) and 8.77 (95 % CI: 5.69–13.5) following XBB.1.5, BA.1 and BA.4-5 vaccines, respectively, translating into a 64 % lower adjusted response (geometric mean ratio [GMR] = 0.36, 95 % CI: 0.21–0.6) in the BA.1 arm, and a 75 % lower response (GMR = 0.25, 95 % CI: 0.15–0.43) in the BA.4-5 arm. This suggests that XBB.1.5 vaccination will most likely, result in improved effectiveness against JN.1 compared with other COVID-19 vaccines.

PASC (Post Acute Sequelae of COVID-19) is associated with decreased neutralizing antibody titers in both biological sexes and increased ANG-2 and GM-CSF in females.

Post-acute sequelae of COVID-19 (PASC) or the continuation of COVID-19 (Coronavirus disease 2019) symptoms past 12weeks may affect as many as 30% of people recovering from a SARS-CoV-2 (severe acute respiratory coronavirus 2) infection. The mechanisms regulating the development of PASC are currently not known; however, hypotheses include virus reservoirs, pre-existing conditions, microblood clots, immune dysregulation, as well as poor antibody responses. Importantly, virus neutralizing antibodies are essential for COVID-19 recovery and protection from reinfection but there is currently limited information on these immune regulators and associated cytokines in PASC patients. Understanding the key drivers of general and specific symptoms associated with Long COVID and the presence of virus neutralizing antibodies in PASC will aid in the development of therapeutics, diagnostics, and vaccines which currently do not exist. We designed a cross-sectional study to investigate systemic antibody and cytokine responses during COVID-19 recovery and PASC. In total, 195 participants were recruited in one of four groups: (1) Those who never had COVID-19 (No COVID); (2) Those in acute COVID-19 recovery (Acute Recovery) (4-12weeks post infection); (3) Those who recovered from COVID-19 (Recovered) (+ 12weeks from infection); and (4) those who had PASC (PASC) (+ 12weeks from infection). Participants completed a questionnaire on health history, sex, gender, demographics, experiences with COVID-19 acute and COVID-19 recovery/continuing symptoms. Serum samples collected were evaluated for antibody binding to viral proteins, virus neutralizing antibody titers, and serum cytokine levels using Ella SimplePlex Immunoassay™ panels. We found participants with PASC reported more pre-existing conditions (e.g. such as hypertension, asthma, and obesity), and PASC symptoms (e.g. fatigue, brain fog, headaches, and shortness of breath) following COVID-19 than COVID-19 Recovered individuals. Importantly, we found PASC individuals to have significantly decreased levels of neutralizing antibodies toward both SARS-CoV-2 and the Omicron BA.1 variant. Sex analysis indicated that female PASC study participants had sustained antibody levels as well as levels of the inflammatory cytokines GM-CSF and ANG-2 over time following COVID-19. Our study reports people experiencing PASC had lower levels of virus neutralizing antibodies; however, the results are limited by the collection time post-COVID-19 and post-vaccination. Moreover, we found females experiencing PASC had sustained levels of GM-CSF and ANG-2. With lower levels of virus neutralizing antibodies, this data suggests that PASC individuals not only have had a suboptimal antibody response during acute SARS-CoV-2 infection but may also have increased susceptibility to subsequent infections which may exacerbate or prolong current PASC illnesses. We also provide evidence suggesting GM-CSF and ANG-2 to play a role in the sex-bias of PASC. Taken together, our findings maybe important for understanding immune molecular drivers of PASC and PASC subgroups.

Additional Insertion of gC Gene Triggers Better Immune Efficacy of TK/gI/gE-Deleted Pseudorabies Virus in Mice.

In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 106.0 TCID50 dose after 4 and 6 weeks post-initial immunization (PII) (p < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 105.0 TCID50 dose after 6 weeks PII (p < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 105.0 TCID50, the level of NA was close to that in the triple-gene deletion virus group with 106.0 TCID50 at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 106.0 TCID50. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 105.0 TCID50, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.

The contributions of vaccination and natural infection to the production of neutralizing antibodies against the SARS-CoV-2 prototype strain and variants

ObjectivesTo evaluate the neutralizing antibody (NAb) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. MethodsThe NAbs against the different viral strains of 490 individuals with SARS-CoV-2 and 187 without SARS-CoV-2 in the Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. ResultsIn uninfected individuals, limited levels of NAbs were produced against the prototype and variant strains after two doses vaccine but significantly increased after three or four doses of the vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. ConclusionsThe immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.

Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery.

Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.

Immunogenicity and safety of a recombinant COVID-19 vaccine (ZF2001) as heterologous booster after priming with inactivated vaccine in healthy children and adolescents aged 3-17 years: an open-labeled, single-arm clinical trial

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023)

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.

Dry and liquid formulations of IBT-V02, a novel multi-component toxoid vaccine, are effective against Staphylococcus aureus isolates from low-to-middle income countries.

Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis, surgical site infections, osteomyelitis, and pneumonia. These infections are exacerbated by the emergence of antibiotic-resistant clinical isolates such as methicillin-resistant S. aureus (MRSA), highlighting the need for alternatives to antibiotics to treat bacterial infections. We have previously developed a multi-component toxoid vaccine (IBT-V02) in a liquid formulation with efficacy against multiple strains of Staphylococcus aureus prevalent in the industrialized world. However, liquid vaccine formulations are not compatible with the paucity of cold chain storage infrastructure in many low-to-middle income countries (LMICs). Furthermore, whether our IBT-V02 vaccine formulations are protective against S. aureus isolates from LMICs is unknown. To overcome these limitations, we developed lyophilized and spray freeze-dried formulations of IBT-V02 vaccine and demonstrated that both formulations had comparable biophysical attributes as the liquid formulation, including similar levels of toxin neutralizing antibodies and protective efficacy against MRSA infections in murine and rabbit models. To enhance the relevancy of our findings, we then performed a multi-dimensional screen of 83 S. aureus clinical isolates from LMICs (e.g., Democratic Republic of Congo, Palestine, and Cambodia) to rationally down-select strains to test in our in vivo models based on broad expression of IBT-V02 targets (i.e., pore-forming toxins and superantigens). IBT-V02 polyclonal antisera effectively neutralized toxins produced by the S. aureus clinical isolates from LMICs. Notably, the lyophilized IBT-V02 formulation exhibited significant in vivo efficacy in various preclinical infection models against the S. aureus clinical isolates from LMICs, which was comparable to our liquid formulation. Collectively, our findings suggested that lyophilization is an effective alternative to liquid vaccine formulations of our IBT-V02 vaccine against S. aureus infections, which has important implications for protection from S. aureus isolates from LMICs.

Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines

Inactivated coronavirus disease 2019 (COVID-19) vaccines such as CoronaVac and BBIBP-CorV have been widely used in China. However, more investigation is still needed to understand antibodies' duration and effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the real world. In this study, 575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited. Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2 (original strain, Dela, and Omicron). Unsurprisingly, a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants. However, despite a booster dose, the neutralizing antibody levels against Omicron, particularly the BA.5.2 subvariant, remained low. There was no sex bias, but an age bias was observed. Notably, the predominant IgG subclass antibodies were IgG1 and IgG2, with a much lower level of IgG4. After the booster shot, the ratio of IgG4 to IgG1 significantly increased. The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses. Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12–17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination

Heterologous Sinovac-CoronaVac booster(s) in 12–17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Utility of COVID-19 Seropositive Plasma as Convalescent Plasma: An Immune and Neutralization Antibody Seroprevalence Analysis in Blood Donors for Future Potential Pandemic Readiness.

To analyze the seroprevalence of SARS-CoV-2 IgG antibodies and neutralizing antibodies in blood donors during the second wave of the pandemic and to explore the utility of COVID-19 seropositive plasma as convalescent plasma. In this study, 696 blood donors were tested for anti-SARS-CoV-2 IgG antibodies using a chemiluminescence assay. By blinding, 271 samples were chosen randomly for testing of neutralizing antibodies by enzyme-linked immunosorbent assay (ELISA) in duplicate among the 696 blood donors tested for anti-SARS-CoV-2 IgG antibodies, irrespective of the positivity or negativity of the result of the anti-SARS-CoV-2 IgG antibodies by chemiluminescence assay.IgG antibody levels were analyzed in signal-to-cutoff (S/Co), while neutralizing antibody levels were analyzed in percentage inhibition. The seroprevalence of IgG antibodies based on the S/Co for the positive results ≥ 1.00 was 82.75%, while the seroprevalence of neutralizing antibodies based on the percentage inhibition for the positive results ≥ 30% was 89.59%. Frontline workers (FLWs) and Covishield-vaccinated individuals showed higher levels of the anti-SARS-CoV-2 IgG antibodies regarding higher S/Co. In comparison, levels of neutralization antibodies regarding percentage inhibition were higher only in FLWs.Covishield-vaccinated donors elicited a statistically higher seroprevalence of anti-SARS-CoV-2 IgG antibodies compared to the Covaxin-vaccinated, while the seroprevalence of neutralizing antibodies was not statistically different among this group. There was a positive correlation (0.762) between anti-SARS-CoV-2 IgG antibodies and neutralizing antibodies, and almost all donors'of S/Co ≥ 9.5 had neutralizing antibodies. This study showed higher seroprevalence in the blood donor population compared to published seroprevalence in India's second wave of the pandemic. In the current study, 328 donors (47.12%) of the 696 screened donors were neither vaccinated nor had previous SARS-CoV-2 infection, but many had antibodies. The seroprevalence of neutralizing antibodies (96.42%) was higher than the seroprevalence of the anti-SARS-CoV-2 IgG antibodies (85.71%) in the donors who had previous infection of COVID-19. On the other hand, vaccinated donors showed similar immune responses for neutralizing antibodies and the anti-SARS-CoV-2 IgG antibodies. Higher IgG immune reactivity in S/Co showed a good correlation with neutralizing antibodies and can be used to screen whole blood donors for convalescent plasma donations.