Difference In Seroconversion Rates Research Articles

Safety, efficacy and immunogenicity of aerosolized Ad5-nCoV COVID-19 vaccine in a non-inferiority randomized controlled trial

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Immunogenicity and Safety of a Quadrivalent Influenza Vaccine in Population Aged 3 Years and Older in Chile and the Philippines: A Phase 3, Non-Inferiority, Double-Blind, Randomized Controlled Clinical Trial.

In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra®) in a population aged 3 years and older in Chile and the Philippines. A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (-0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable.

Immunological and Safety Considerations When Selecting the Dose Formulation of a Purified Inactivated Zika Virus Vaccine (PIZV).

We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 months post-vaccination) and discuss considerations (e.g., immunological, historic, flavivirus immunological cross-reactions) for selecting a Zika virus (ZIKV) vaccine dose formulation. TAK-426 dose selection was conducted at the first interim analysis, and was based on cumulative safety data from both flavivirus-naïve (up to ≥28 days post-dose PD2) and flavivirus-primed participants (up to ≥28 days PD1), and on immunogenicity data from flavivirus-naïve participants only (at 28 days PD1 and 28 days PD2). The safety profile from TAK-426 recipients was compared to placebo recipients. Immunogenicity was assessed by geometric mean titer ratios of neutralizing anti-ZIKV antibodies and differences in seroconversion rates. There was no significant difference in safety between the three TAK-426 doses. The 10 μg dose provided the earliest and strongest immune response (with close to 100% seroconversion and higher antibody titers PD1 in flavivirus-naïve participants), and was well tolerated with acceptable safety profiles in both flavivirus-naïve and flavivirus-primed participants; this dose was selected for further development.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial

In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods. We aimed to evaluate the immunogenicity and safety of Euvichol-S (EuBiologics, Seoul, South Korea) compared with an active control vaccine, Shanchol (Sanofi Healthcare India, Telangana, India) in participants of various ages in Nepal. We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Nepal. Eligible participants were healthy individuals aged 1-40 years without a history of cholera vaccination. Individuals with a history of hypersensitivity reactions to other preventive vaccines, severe chronic disease, previous cholera vaccination, receipt of blood or blood-derived products in the past 3 months or other vaccine within 4 weeks before enrolment, and pregnant or lactating women were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block sizes of two, four, six, or eight) to one of four groups (groups A-D); groups C and D were stratified by age (1-5, 6-17, and 18-40 years). Participants in groups A-C were assigned to receive two 1·5 mL doses of Euvichol-S (three different lots) and participants in group D were assigned to receive the active control vaccine, Shanchol. All participants and site staff (with the exception of those who prepared and administered the study vaccines) were masked to group assignment. The primary immunogenicity endpoint was non-inferiority of immunogenicity of Euvichol-S (group C) versus Shanchol (group D) at 2 weeks after the second vaccine dose, measured by the seroconversion rate, defined as the proportion of participants who had achieved seroconversion (defined as ≥four-fold increase in V cholerae O1 Inaba and Ogawa titres compared with baseline). The primary immunogenicity endpoint was assessed in the per-protocol analysis set, which included all participants who received all their planned vaccine administrations, had no important protocol deviations, and who provided blood samples for all immunogenicity assessments. The primary safety endpoint was the number of solicited adverse events, unsolicited adverse events, and serious adverse events after each vaccine dose in all ages and each age stratum, assessed in all participants who received at least one dose of the Euvichol-S or Shanchol. Non-inferiority of Euvichol-S compared with Shanchol was shown if the lower limit of the 95% CI for the difference between the seroconversion rates in Euvichol-S group C versus Shanchol group D was above the predefined non-inferiority margin of -10%. The trial was registered at ClinicalTrials.gov, NCT04760236. Between Oct 6, 2021, and Jan 19, 2022, 2529 healthy participants (1261 [49·9%] males; 1268 [50·1%] females), were randomly assigned to group A (n=330; Euvichol-S lot number ES-2002), group B (n=331; Euvichol-S ES-2003), group C (n=934; Euvichol-S ES-2004]), or group D (n=934; Shanchol). Non-inferiority of Euvichol-S versus Shanchol in seroconversion rate for both serotypes at 2 weeks after the second dose was confirmed in all ages (difference in seroconversion rate for V cholerae O1 Inaba -0·00 [95% CI -1·86 to 1·86]; for V cholerae O1 Ogawa -1·62 [-4·80 to 1·56]). Treatment-emergent adverse events were reported in 244 (9·7%) of 2529 participants in the safety analysis set, with a total of 403 events; 247 events were reported among 151 (9·5%) of 1595 Euvichol-S recipients and 156 events among 93 (10·0%) of 934 Shanchol recipients. Pyrexia was the most common adverse event in both groups (57 events among 56 [3·5%] of 1595 Euvichol-S recipients and 37 events among 35 [3·7%] of 934 Shanchol recipients). No serious adverse events were deemed to be vaccine-related. A two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. The Bill & Melinda Gates Foundation. For the Nepali translation of the abstract see Supplementary Materials section.

A randomized, blind, parallel controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of 23-valent pneumococcal polysaccharide vaccine in healthy people aged 2 years and older

BackgroundDespite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. MethodsAll subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0–7 days and 8–28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). ResultsThe most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. ConclusionThis clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to

Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of circulating vaccine-derived polioviruses. This trial aimed to provide key safety and immunogenicity data required for nOPV2 licensure and WHO prequalification. This phase 3 trial recruited infants aged 18 to <52 weeks and young children aged 1 to <5 years in The Gambia. Infants randomly assigned to receive one or two doses of one of three lots of nOPV2 or one lot of bivalent OPV (bOPV). Young children were randomised to receive two doses of nOPV2 lot 1 or bOPV. The primary immunogenicity objective was to assess lot-to-lot equivalence of the three nOPV2 lots based on one-dose type 2 poliovirus neutralising antibody seroconversion rates in infants. Equivalence was declared if the 95% CI for the three pairwise rate differences was within the -10% to 10% equivalence margin. Tolerability and safety were assessed based on the rates of solicited adverse events to 7 days, unsolicited adverse events to 28 days, and serious adverse events to 3 months post-dose. Stool poliovirus excretion was examined. The trial was registered as PACTR202010705577776 and is completed. Between February and October, 2021, 2345 infants and 600 young children were vaccinated. 2272 (96·9%) were eligible for inclusion in the post-dose one per-protocol population. Seroconversion rates ranged from 48·9% to 49·2% across the three lots. The minimum lower bound of the 95% CIs for the pairwise differences in seroconversion rates between lots was -5·8%. The maximum upper bound was 5·4%. Equivalence was therefore shown. Of those seronegative at baseline, 143 (85·6%) of 167 (95% CI 79·4-90·6) infants and 54 (83·1%) of 65 (71·7-91·2) young children seroconverted over the two-dose nOPV2 schedule. The post-two-dose seroprotection rates, including participants who were both seronegative and seropositive at baseline, were 604 (92·9%) of 650 (95% CI 90·7-94·8) in infants and 276 (95·5%) of 289 (92·4-97·6) in young children. No safety concerns were identified. 7 days post-dose one, 78 (41·7%) of 187 (95% CI 34·6-49·1) infants were excreting the type 2 poliovirus. nOPV2 was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2. Bill & Melinda Gates Foundation.

Comparative immunogenicity and safety of SpikoGen®, a recombinant SARS-CoV-2 spike protein vaccine in children and young adults: An immuno-bridging clinical trial

BackgroundSpikoGen® is a recombinant subunit spike protein ectodomain vaccine manufactured in insect cells and formulated with the novel polysaccharide-based Advax-CpG55.2 adjuvant. This study aimed to compare the immunogenicity and safety of SpikoGen® vaccine in children, adolescents and young adults. MethodsThis was a non-randomized, three-arm, open-label, parallel-group, immuno-bridging, non-inferiority trial to compare the immunogenicity and safety of a primary course of two intramuscular doses of SpikoGen® vaccine in children aged 5 to < 12 years, adolescents aged 12 to < 18 years and young adults aged 18 to 40 years. Children 5–12 years received a half dose of 12.5 μg spike protein, whereas the other groups received the full vaccine dose. Vaccine immunogenicity was evaluated via assessment of serum anti-spike and neutralizing antibodies 14 days after the second dose. Solicited adverse events were recorded for 7 days after each vaccination. Safety assessments including serious adverse events were continued through six months after the second dose in children and adolescents. ResultsTwo weeks after the second dose, seroconversion rates for neutralizing antibody levels were not significantly different for children (59.50 %), adolescents (52.06 %) and adults (56.01 %). The 95 % confidence interval of the difference in seroconversion rates between children and adults was within the prespecified non-inferiority margin of 10 % (−12 % to 5 %). SpikoGen® vaccine was well tolerated in all age groups with the most common solicited adverse events being injection site pain and fatigue which were generally transient and mild. ConclusionSpikoGen® vaccine was shown to be safe, well tolerated and immunogenic in children as young as 5 years of age, with non-inferior responses to those seen in adults. The Iranian FDA authorisation of SpikoGen® vaccine is now extended down to 5 years of age.

Safety and immunogenicity of a serum-free purified Vero rabies vaccine in comparison with the rabies human diploid cell vaccine (HDCV; Imovax® Rabies) administered in a simulated rabies post-exposure regimen in healthy adults

A new generation, serum-free, antibiotic-free, purified Vero rabies vaccine (PVRV-NG; Sanofi) has been developed based on the same Pitman-Moore viral strain used for the currently licensed purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi) and human diploid cell vaccine (HDCV; Imovax® Rabies, Sanofi). PVRV-NG has demonstrated a satisfactory safety profile and induces robust immune responses, with non-inferiority demonstrated versus PVRV when given as a three-dose pre-exposure prophylaxis (PrEP) regimen in healthy children and adults. Here, we evaluated the safety and immunogenic non-inferiority of PVRV-NG compared to HDCV when administered as simulated post-exposure prophylaxis (PEP), with concomitant administration of human rabies immunoglobulin (HRIG), in healthy adults in the USA. Participants were vaccinated according to the 5-dose Essen intramuscular regimen (4-week, 1-injection site regimen, with a single dose given on days 0, 3, 7, 14 and 28) for PEP, with concomitant HRIG administered on day 0. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 14, 28 and 42. Non-inferiority of PVRV-NG compared with HDCV was shown if the lower limit of the 95 % confidence interval (CI) for the difference in seroconversion rates (RVNA titers ≥ 0.5 IU/mL on day 14) between PVRV-NG and HDCV was above the non-inferiority margin of –5 %. Safety was evaluated after each vaccination and monitored throughout the study. The difference in seroconversion rate between the PVRV-NG and HDCV groups was –2.8 % (95 % CI, –8.08 to 4.20), indicating that non-inferiority was not demonstrated. The seroconversion rate was < 99 % in both study groups on day 14. There were no major safety concerns identified, and PVRV-NG demonstrated a similar safety profile to HDCV.

Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR=1.05, 95%CI 1.01-1.10, P=0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR=0.95, 95% CI 0.89-1.01, P=0.09) or with cancer patients receiving targeted therapy (RR=1.05, 95% CI 0.79-1.39, P=0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

Immunogenicity and Safety of MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared with a Nonadjuvanted, Quadrivalent Influenza Vaccine in Adults 50-64 Years of Age.

Adults aged 50-64 years have a high incidence of symptomatic influenza associated with substantial disease and economic burden each year. We conducted a randomized, controlled trial to compare the immunogenicity and safety of an adjuvanted quadrivalent inactivated influenza vaccine (aIIV4; n = 1027) with a nonadjuvanted standard dose IIV4 (n = 1017) in this population. Immunogenicity was evaluated on Days 22, 181, and 271. On Day 22, upper limits (UL) of 95% confidence intervals (CI) for geometric mean titer (GMT) ratios (IIV4/aIIV4) were <1.5 and 95% CI ULs for the difference in seroconversion rate (SCR IIV4 - aIIV4) were <10% for all four vaccine strains, meeting primary endpoint noninferiority criteria. Protocol-defined superiority criteria (95% CI ULs < 1.0) were also met for A(H1N1) and A(H3N2). Immune responses following aIIV4 vaccination were more pronounced in persons with medical comorbidities and those not recently vaccinated against influenza. Safety data were consistent with previous studies of MF59 adjuvanted seasonal and pandemic influenza vaccines. These findings support the immunological benefit of aIIV4 for persons aged 50-64 years, especially those with comorbidities.

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18–26 years in China: a randomised blinded clinical trial

An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9. This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed. From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243]). Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries. National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax.

Immunogenicity after COVID-19 vaccination in patients with solid tumor and hospital staff: A prospective single-center observational study.

10626 Background: Patients with tumor are at high risk of severe COVID-19, and vaccination against SARS-CoV-2 is recommended. Impact of cancer treatment on immunogenicity has not been evaluated well. Methods: This prospective study was conducted to assess the seroconversion rate of SARS-CoV-2 vaccines among patients with cancer and hospital staff. Further, we focused on the difference among cancer treatment regimens. SARS-CoV-2 spike protein-specific IgG (S-IgG) were evaluated before the first vaccination, 1–3 months, 4–6 months, and 7–12 months after the second vaccination, and 1–3 months after the third vaccination. The primary endpoint was seroconversion rate measured 1–3 months after the second vaccination. Results: From April 2021 to November 2021, consent was obtained from 629 cancer patients and 210 hospital staff. Excluding missing data and withdrawal of consent, 590 cancer patients and 183 hospital staff without complications was analyzed. At 1–3 months after the second vaccination, S-IgG antibody concentration higher than the cut-off value (20 BAU/mL) was found in 96.1% (567/590) patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4–6 months after second vaccination, S-IgG antibody concentration higher than the cut-off value was found in 93.1% (461/495) patients with cancer and 100% (170/170) of the healthy controls (p &lt; 0.0001). The significant difference in seroconversion rate between the two groups persisted even after 7-12 months. Patients undergoing treatment regimens such as platinum combination therapy (median: 423.7, 95% CI: 264.2–767.0, p = 0.003) and alkylating agent (median: 57.5, 95% CI: 5.4–748, p &lt; 0.0001) among cytotoxic drugs, and PARP inhibitor (median: 264, 95% CI: 43–690.4, p = 0.0004), mTOR inhibitor (median: 227.4, 95% CI: 5.7–323.4, p = 0.0036), BCR-ABL inhibitor among drugs (median: 124.4, 95% CI: 0.0–288.9, p = 0.005) among target molecule drugs showed lower antibody titer compared to the no-treatment patients with cancer group. Conclusions: SARS-CoV-2 vaccine immunogenicity was low among patients with cancer compared to healthy control. Also, several treatment regimens were found to negatively impact immune response. Clinical trial information: UMIN000049403 , UMIN000049430 . [Table: see text]

Effect of Moderate to Severe Hepatic Steatosis on Vaccine Immunogenicity against Wild-Type and Mutant Virus and COVID-19 Infection among BNT162b2 Recipients.

We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking. Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use. Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24). NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.

COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE.MethodsThe objective...

Serological Response after Two Doses of Sars-Cov-2 Vaccines in CML Patients - a Prospective Study of a Brazilian Center

COVID-19 is associated with a worse prognosis in patients with hematologic malignancies. The mortality rate of CML patients with COVID-19 was 5,5 - 13% before COVID-19 vaccination was available. There are few studies about the efficacy of SARS-CoV-2 vaccines in this population. Objectives This study aimed to evaluate the seroconversion rates after two doses of SARS-CoV-2 vaccines in chronic myeloid leukemia (CML) patients who were receiving tyrosine kinase inhibitors (TKIs) or in treatment-free-remission (TFR). Methods Peripheral blood samples were collected from CML patients 1 to 3 months after two doses of SARS-CoV-2 vaccines to perform a qualitative screening serologic test (CMIA, SARS-CoV-2 IgM, IgG - Alinity System, Abbott Laboratories, Ireland). Samples from the reactive tests underwent a second analysis through quantitative IgG (anti-S1) assessment (SARS-CoV-2 IgG II Quant, Alinity System, Abbott Laboratories, Ireland) and for neutralizing antibody titers (nAbs), which detects the cytopathic effect of the virus in culture (Vero CCL-81 cells) elicited by the vaccines. Results Between August and November 2021, 102 CML patients were evaluated. The median age was 56,2 years (33-85), 58,8% were male, and 40,2% had at least one comorbidity. 98% of the patients were in the chronic phase (CP), and 80% had at least a major molecular response (MMR); 87% received TKI, and 13% were in treatment-free remission (TFR). Among 102 patients, 66,7% received ChAdOx1 nCoV-19 (AZD1222)-Covishield (Oxford/AstraZeneca/Fiocruz) vaccine, 29,41% CoronaVac (Sinovac/Butatan) vaccine, 1,96% BNT162b2 (Pfeizer/BioNTech/Fosun Pharma) vaccine and 1,96% Ad26.COV2.S (Janssen-Cilag) COVID-19 vaccine. Fifteen % had mild COVID-19 before vaccination. A screening qualitative serologic test (CMIA) was positive in 26/102 (25%) patients. COVID-19 before vaccination was associated with IgG antibody positivity (p<=0.001). nAbs titers were higher than 1:320 in 13/26 cases; 5 had COVID-19 before completing the vaccination scheme. Patients received ChAdOx1 nCoV-19 vaccine (76%), Coronavac (19%) and BNT162b2 (1%). There were 7 COVID-19 confirmed cases and two suspected. Eight cases occurred before vaccination, and one presented a mild COVID-19 after ChAdOx1 nCoV-19's first dose. Eleven were treated with imatinib (first line), six patients with dasatinib and one with nilotinib (second-line, 6 with MMR), 5 in third or fourth line (no MMR) and three patients were in TFR. The proportion of patients with nAbs > 1:320 was superior in the group receiving a third or fourth line (p=0.022). Seroconversion rates (CMIA, IgM and IgG) between CoronaVac and ChAdOx1 nCoV-19 were not statistically significant. There was no difference in seroconversion rates according to the patient's age or in those treated with TKI or in TFR (p=0.77). Conclusions In the present study, the serological response of CML patients after two vaccine doses was lower than observed in the general population, reinforcing the importance of the third dose. No differences were identified between the vaccine type (Coronavac vs. ChAdOx1 nCoV-19). nAbs titers were higher in the group treated in the third or fourth line. However, this group had more patients with COVID-19 prior to vaccination. Therefore, further studies are necessary to evaluate if TKI treatment could interfere with the vaccine's efficacy.

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

SummaryBackgroundThe enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration.MethodsWe conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345).FindingsBetween June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines.InterpretationEV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated.FundingHubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

Immunogenicity and safety of the inactivated enterovirus 71 vaccine administered concomitantly with the measles-rubella vaccine in infants aged 8 months in China: A noninferiority randomized controlled trial

BackgroundTo evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine. MethodsIn this phase 4, randomized, open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups. ResultsAfter vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of −10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group). ConclusionAntibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles.

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age

SummaryTrial DesignPhase 3, randomized, controlled, multicenter, equivalence trial.MethodsRecruitment of participants occurred between 04Februray2020 and 15July2020 at four centers in the Philippines: University of the East – Ramon Magsaysay Memorial Medical Center Inc., Quezon City; University of Philippines Manila – National Institute of Health, Ermita Manila; Asian Hospital and Medical Center, Metro Manila, Philippines Study; and Medical Research Unit, Tropical Disease Foundation, Makati City, Metro Manila, Philippines.Participants1800 adults and children 6-months to 45-years of age.InterventionsParticipants received a single injection of multidose (MD) or single dose (SD) Vi-DT as test vaccines or meningococcal conjugate vaccine as a comparator.ObjectiveTo evaluate immune equivalence of SD and MD formulations of Vi-DT, and to assess the safety of both formulations compared with comparator vaccine.Outcome MeasurementBlood draw for immunogenicity was performed at baseline prior to vaccine receipt and at four weeks after vaccination for a subset of participants to determine anti-Vi IgG geometric mean titers (GMT) and seroconversion rates. The primary outcome was comparison of anti Vi-IgG seroconversion and GMT between the two formulations of Vi-DT at 4 weeks following vaccine administration. Immune equivalence of MD and SD formulations was confirmed when the two-tailed 95% confidence interval (CI) of the GMT ratio is within [0.67, 1.5] at a two-sided significance level of 0.05. All participants were followed for safety events for six months after vaccine administration.RandomizationParticipants were randomized to receive SD Vi-DT, MD Vi-DT, or meningococcal conjugate vaccines in 2.5:2.5:1 allocation ratio.BlindingStudy participants and observers were blinded to treatment assignment.FindingsImmune equivalence of SD (n=252) and MD (n=247) formulations was confirmed by anti-Vi IgG GMT ratio of 1.14 (95%CI: 0.91, 1.43) with respective GMTs in the MD and SD groups of 640.62 IU/mL (95%CI: 546.39, 751.11) and 562.57 IU/mL (95%CI: 478.80, 661.00) (p=0.259). Similarly, anti-Vi IgG seroconversion rate difference between the two formulations of ‒0.43% (95%CI: –4.42, 3.56) confirmed immune equivalence with corresponding seroconversion rates of 98.38% (95%CI: 95.91, 99.37) and 98.81% (95%CI: 96.56, 99.59) in MD and SD Vi-DT formulations, respectively (p=0.722). Both formulations of Vi-DT had a satisfactory safety profile – all five serious adverse events reported during the study were unrelated to the investigational product.InterpretationThe MD and SD formulations of Vi-DT elicited robust and equivalent immune responses following one dose vaccination, and both formulations demonstrated a favorable safety profile.Trial RegistrationClinicalTrials.gov: NCT04204096.FundingThis study was funded by the Bill & Melinda Gates Foundation (OPP 1115556).

Effect of moderate-to-severe hepatic steatosis on neutralising antibody response among BNT162b2 and CoronaVac recipients.

Background/AimsStudies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects.MethodsTwo hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56.ResultsFor BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036).ConclusionsWhile there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.

Neutralizing Antibody Response to BBIBP-CorV in Comparison with COVID-19 Recovered, Unvaccinated Individuals in a Sample of the Pakistani Population.

Fifty five percent of the Pakistani population is still unvaccinated with the two-dose protocol of COVID-19 vaccines. This study was undertaken to determine the seroconversion rate and antibody titers following the two-dose BBIBP-CorV protocol, and to compare these variables in unvaccinated, COVID-19 recovered individuals (total n = 180) at Indus Hospital and Health Network, Karachi. Pseudotyped lentivirus antibody neutralization assays and SARS-CoV-2 IgG Quant II (Abbott) immunoassays were performed 4-8 weeks following the second dose of the BBIBP-CorV or PCR positivity/onset of symptoms of COVID-19. Seroconversion rate, using neutralization assays, in vaccinated individuals was lower (78%) than that in unvaccinated, COVID-19-recovered individuals with moderate to severe infection (97%). Prior PCR positivity increased serocoversion rate to 98% in vaccinated individuals. Immunoassays did not, however, reveal significant inter-group differences in seroconversion rates (≥95% in all groups). Log10 mean antibody neutralizing titers following the two-dose BBIBP-CorV protocol (IC50 = 2.21) were found to be significantly less than those succeeding moderate to severe COVID-19 (IC50 = 2.94). Prior SARS-CoV-2 positivity significantly increased post-vaccination antibody titers (IC50 = 2.82). Similar inter-group titer differences were obtained using the immunoassay. BBIBP-CorV post-vaccination titers may, thus, be lower than those following natural, moderate to severe infection, while prior SARS-CoV-2 exposure increases these titers to more closely approximate the latter.