Human Vaccines & Immunotherapeutics

Four principal types of authorised COVID-19 vaccines include inactivated whole-virus vaccines, protein subunit vaccines, viral-vector vaccines and nucleic acid (mRNA and DNA) vaccines. Despite numerous Randomised Controlled Trials (RCTs), comprehensive systematic review and comparative meta-analysis have not been performed to validate the immunogenicity, safety and efficacy of COVID-19 vaccines in the healthy adult population. We aim to fulfil this unmet void. We searched for peer-reviewed articles about RCTs of the COVID-19 vaccines on healthy adults (18-64 years) available in eight major bibliographic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, ScienceDirect, POPLINE, HINARI) till August 28, 2022. The Risk of Bias (RoB) was assessed using the Cochrane RoB-2. Random effects meta-analysis was conducted by pooling dichotomous outcomes using risk ratios (safety outcomes) and continuous outcomes using standardised mean differences (immunogenicity outcomes). Efficacy outcomes were summarised narratively. Moderate to high-quality evidence suggests that those receiving COVID-19 vaccines had significantly higher immune responses compared to placebo. Serious adverse events were rare, confirming that COVID-19 vaccines were safe and immunogenic for the healthy adult population. Remarkably, adverse events were the least common in inactivated vaccines, and nucleic acid vaccines were the most immunogenic. The efficacies of COVID-19 vaccines ranged from 21.9% to 95.9% in preventing COVID-19. We endorse all four types of COVID-19 vaccines for public health policy implementing taskforces. Yet, meta-analyses based on individual patient data are warranted for more extensive measurement of differential impacts of COVID-19 vaccines on different genders, ethnicities, comorbidities and types of vaccine jabbed.

BackgroundThe availability of an effective vaccine does not equate to its use; its effectiveness primarily depends on vaccine acceptance by the targeted population. Despite the rapid development and widespread access to the COVID-19 vaccine, herd immunity is yet to be achieved, with vaccine hesitancy as a major barrier. This study sought to systematically assess the beliefs, attitudes, and acceptance towards COVID-19 vaccines, including factors contributing to vaccination hesitancy in the Eastern and Western hemispheres. MethodsA comprehensive search of articles was conducted through Scopus, PubMed, Embase, CINAHL, Cochrane CENTRAL, and Web of Science databases for studies published from inception to May 2023 using the PRISMA guidelines. ResultsOur search yielded 1154, of which 21 were eligible for inclusion. The rate of willingness or intention to vaccinate varied with the geographic region, from 12% in the USA to 93.9% in China. Four studies from the Western and two from Eastern regions reported a low acceptance rate (defined as <50%): USA (12%), Spain (48.3%), Switzerland (38.6%), Europe (multi-national, 31%), Nepal (38.3%), and Oman (43%). Overall, vaccine acceptance was low-to-moderate in the general population and healthcare workers (HCWs) in both Eastern and Western hemispheres except for China which reported high acceptance (defined as >75%) among the general population and HCWs. Demographic characteristics (female, younger age, and higher education) and non-demographic factors (knowledge about the COVID-19 vaccine and its development, history of influenza vaccination, perceived susceptibility or severity of infection, and the belief that vaccines are effective in controlling the pandemic were associate with high acceptance rates or intentions to take the COVID-19 vaccine. On the other hand, mistrust of the vaccine, its safety and effectiveness, disinformation or poor awareness of the vaccine, side effects concerns, belief in natural immunity, previous adverse experience with the vaccines, and distrust in the information sources about the COVID-19 pandemic were associated with vaccination hesitancy. ConclusionFor better acceptance, COVID-19 vaccination campaign strategies should be modeled based on regional political, economic, and social contexts. HighlightsO_LIThe willingness to accept COVID-19 vaccines was low-to-moderate in both hemispheres. C_LIO_LIHealthcare workers were as willing to vaccinate as the general population. C_LIO_LIVaccine hesitancy was associated with demographic and vaccine-specific factors. C_LI

IntroductionIn August 2021, Thailand imported the BNT162b2 mRNA COVID-19 vaccine. The prioritised group to receive the BNT162b2 vaccine were health professionals. The BNT162b2 vaccine scheduled for healthcare workers were two-dose regimen administered three weeks apart, the third dose booster in two-dose inactivated CoronaVac vaccine recipients or as a second dose in health professionals who had received the CoronaVac or adenoviral-vectored (ChAdOx1-S) vaccine as the first dose regardless of the interval between the first and second dose. MethodsThis study aims to evaluate the immunogenicity of the heterologous prime boost CoronaVac followed by BNT162b2 in health professionals. ResultsThe CoronaVac/BNT162b2 vaccine recipients elicited higher neutralizing activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. ConclusionsThe heterologous CoronaVac/BNT162b2 could be used as an alternative regimen in countries experiencing the vaccine shortages and in individuals experiencing the adverse events following CoronaVac.

ObjectiveTo report the safety and immunogenicity profile of a protein subunit vaccine (Covovax) given as a third (booster) dose to individuals primed with different primary vaccine regimens. MethodsIndividuals primed with two doses of COVID-19 vaccines for at least 3 months were enrolled and assigned to five groups according to their primary vaccine regimens: CoronaVac, BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell response. ResultsOverall, 215 individuals were enrolled and boosted with the Covovax vaccine. The reactogenicity achieved was mild-to-moderate. Most participants elicited a high level of binding and neutralizing antibody responses against wild type and omicron variants following the booster dose. The 197 participants were classified by anti-N IgG. Of these, 141/197 (71.6%) were a seronegative population, and neutralizing activity and IFN-{gamma} release were further monitored. A booster dose could elicit neutralizing activity to wild type and omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The Covovax vaccine could elicit a cell-mediated immune response. ConclusionThe protein subunit vaccine (Covovax) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.

The objective of this review is to give an overall view of COVID-19 bivalent vaccines knowledge and to explore their early available real world effectiveness evidence in the Omicron era. Presently, bivalent vaccines are generally offered to all groups eligible for their next booster, as defined by the national vaccination campaign, with varying policies between countries. The use of bivalent vaccines is supported by immunogenity studies, which, nevetheless, have led to contradictory conclusions, and are not generally designed to measure clinical impact. In order to critically appraise the available research on real world effectiveness, a systematic literature search was performed: out of 876 references examined, 14 studies were finally included and extracted. The findings of this review demonstrate modest to moderate additional protection of vaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines against COVID-19 associated illness and hospitalization, -if compared with having received a monovalent dose as booster-, during a period when BA.5 and other Omicron sublineage viruses predominated globally, Considering the complexity of the current immunity situation at global level, and the high level of heterogeneity both at study and at review level, these findings must be taken with caution. Further research on SARS-CoV-2 vaccine effectiveness against emerging SARS-CoV-2 variants is encouraged.

Limited COVID-19 vaccines in many countries have delayed mass-immunization. Although individuals fully vaccinated with Vaxzevria (AstraZeneca) have higher antibody levels than those with CoronaVac (Sinovac), heterologous prime-boost with CoronaVac-Vaxzevria yielded comparable antibody levels to two-dose Vaxzevria. Combination use of different available vaccines may be warranted in Thailand, which faces limited vaccine choice and supply.

ObjectiveTo determine the attributes of COVID-19 vaccines that influence vaccine acceptance using a DCE through a systematic review. MethodsA systematic search was carried out for articles published up to November 2021 in the PubMed, Psycinfo, Embase, Web of Science, and Global Index Medicus databases. The electronic search algorithm consisted of the terms (Covid-19) AND (Vaccine) AND (discrete choice experiment). FindingsA total of 39 records were retrieved of which 18 duplicates were identified and removed. Of the remaining 21 records, 10 were excluded because they did not use a DCE approach. 11 studies were included in the meta-analyses with a total of 42 795 participants from three WHO regions. We examined 13 attributes of COVID-19 vaccine that influenced acceptance; cost, vaccine efficacy, number of doses, risk of side effects, proof of vaccination, vaccination setting, duration of immunity, doctors recommendation, proportion of acquaintances vaccinated, region of vaccine manufacture, background knowledge of herd immunity, life attenuated or mRNA, speed of vaccination development. The four attributes reported to influence COVID-19 vaccine preferences most worldwide were; high vaccine efficacy, low risk of side effects, long duration of immunity and low number of doses of the vaccine. ConclusionThe most preferred COVID-19 vaccine attributes should be taken into account by vaccine manufacturers and public health policy makers for better introduction and acceptance of COVID-19 vaccine to the world.

The availability of safe and effective vaccine alone does not save lives; it is the inoculation plus other public health measures that do. Recent reports suggest the growing trend in vaccine preferential bias in parts of the world but not much in Europe. The present paper aims to investigate the occurrence of COVID-19 vaccine preferential bias in Europe for effective vaccination planning and pandemic control. MethodData on vaccine delivered and vaccination campaigns of the EU member states was collected from Eu center for disease control (EUCDC) on COVID-19 vaccination radar. The data was processed for analysis on MS excel and both descriptive and statistical analysis was done with IBMs SPSS version 21. Analysis was performed at 95% confidence interval and statistically significant difference was considered at p < 0.05. ResultsWe observed statistically significantly lower vaccine uptake compared to the vaccine delivered doses in the present study (average at 62.678 +/-3.928%) (p< 0.05, CI = 95%). Great variances in uptake for Oxford-AstraZeneca vaccines (50.927 +/-4.626 %) compared to Pfizer-Biontech vaccine (86.285 +/- 2.1052 %) was observed compared to previous prospective study on the wiliness to receive COVID-19 vaccine in the region (75%). ConclusionPublic health practitioners and policy makers need to factor the existence of COVID-19 preferential bias based on vaccine type or manufacturer. This will enable them introduce policies including public educational campaigns to overcome biasness on the wiliness to inoculate thereby enhancing vaccine uptake for smooth and effective control of the pandemic.

BackgroundIn the current protracted COVID-19 pandemic, SARS-CoV-2 vaccines that have the ability to be used safely and to prevent onset or severe disease are still highly needed. A Phase 1/2 study was conducted in healthy adults and the elderly in Japan to evaluate the immunogenicity, safety, and tolerability of an inactivated whole-virus vaccine (KD-414) that is under development. MethodsIn this double-blind, randomized, placebo-controlled, Phase 1/2 study, adults aged 20 to 64 years and elderly participants aged 65 years or older without a history of COVID-19 were randomly allocated to the following groups: the L group (2.5 g/dose), M group (5 g/dose), or H group (10 g/dose) with KD-414, or the placebo group (2:2:2:1). The participants received KD-414 or the placebo intramuscularly twice at intervals of 28 days. To determine the go-forward dose, safety after the first dosing and neutralizing antibody titers against SARS-CoV-2 at 28 days after the second dosing were evaluated for each group. Additionally, after unblinding, participants in the H group received a third dose of KD-414 (H) approximately 6 months after the second dosing for an exploratory evaluation of the safety and neutralizing antibody titers to be conducted. ResultsA total of 210 participants were enrolled: 105 adults aged 20 to 64 years, and 105 elderly participants aged 65 years or older. Of these participants, 105 adults and 104 elderly participants completed the second dosing, and 28 adults and 31 elderly participants in the H group received a third dose of KD-414 (H). The incidence of adverse reactions from the first dosing to 28 days after the second dosing was 19 of 30 (63.3%), 22 of 31 (71.0%), 22 of 29 (75.9%), and six of 15 (40.0%) for adults, and 14 of 30 (46.7%), 14 of 29 (48.3%), 15 of 31 (48.4%), and six of 15 (40.0%) for elderly participants in the L, M, H, and placebo groups, respectively. No differences in incidence were shown among the KD-414 groups. The most common adverse reaction was injection site pain. Fever that resolved the following day was observed in only 1 adult in the H group after the second dosing; this was a sole Grade 3 or higher adverse reaction. For immunogenicity, the neutralizing antibody seroconversion rate (95% confidence intervals [CI]) against SARS-CoV-2 (vaccine strain) 28 days after the second dosing was 36.7% (19.9-56.1), 38.7% (21.8-57.8), and 72.4% (52.8-87.3) in adults, and 33.3% (17.3-52.8), 31.0% (15.3-50.8), and 45.2% (27.3-64.0) in elderly participants in the L, M, and H groups, respectively, showing a dose response by KD-414. The stratified analysis by age-range for the H group, which observed the highest immunogenicity, also showed an age dependency in the neutralizing antibody responses. Based on these results up to the second dosing, the H (10 g/dose) dosage was determined as the recommended dosage for further clinical development of KD-414. In addition, there was no particular difference between the incidence of adverse reactions after the third dosing and that after the second dosing with KD-414 (H) in participants. Moreover, the geometric mean neutralizing antibody titers (GMTs) against SARS-CoV-2 (vaccine strain) 28 days after the third dosing were 2-fold higher than those at 28 days after the second dosing, and the GMTs 13 weeks after the third dosing were 3-fold higher than those at 13 weeks after the second dosing. The stratified analysis by age-range of Pseudovirus SARS-CoV-2 (D614) spike protein neutralizing antibody titers showed 100.0% neutralizing antibody seroconversion rate and high neutralizing antibody titers in participants aged [&le;] 40 years. ConclusionKD-414 was well tolerated in healthy adults and the elderly at all doses evaluated. In view of the dose-response and age-dependency of the immunogenicity of KD-414 (H) (10 g/dose), it is expected to induce high neutralizing antibody titers, particularly in the age range of 20 to 40 years. A Phase 2/3 study (Japan Registry of Clinical Trials [jRCT] 2071210081), a Phase 3 study (jRCT 2031210679), and a Phase 2/3 study in pediatric participants aged 6 months to 17 years (jRCT 2031220032) using KD-414 (H) are ongoing.

BACKGROUNDThe top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODSWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 g/0.5 mL or 6 g /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTSCoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 g dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONSFavorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

BackgroundMany people worldwide have now acquired immune responses against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) following previous vaccination and/or infection. As a result, national vaccination programs are now implementing a simplified schedule of single-dose administration and seasonal boosters. In this phase 3 non-inferiority study, we assessed the immunogenicity and safety of a single dose of the lipid nanoparticle-messenger ribonucleic acid vaccine DS-5670d, a monovalent composition for the 2023/24 season, containing an omicron XBB.1.5-derived antigen. Methods and FindingsAdults and children aged [&ge;]12 years were stratified according to their history of both prior SARS-CoV-2 infection plus prior coronavirus disease 2019 (COVID-19) vaccination (subpopulation A), prior infection only (subpopulation B), prior vaccination only (subpopulation C), or no history of either infection or vaccination (subpopulation D), and randomly assigned (1:1) to receive DS-5670d or monovalent BNT162b2 omicron XBB.1.5. In the combined ABC subpopulations (DS-5670d, n = 362 vs BNT162b2, n = 363), the adjusted geometric mean titer ratio of blood neutralizing activity against SARS-CoV-2 (omicron XBB.1.5) was 1.218 (95% confidence interval [CI], 1.059, 1.401) and the seroresponse rates were 87.3% (DS-5670d) and 82.9% (BNT162b2) with an adjusted difference of 4.5% (95% CI, -0.70, 9.71). Both results exceeded prespecified non-inferiority margins and the study met the primary endpoint. Immunogenicity data in the overall ABCD population also met non-inferiority criteria. There were no apparent differences in immunogenicity according to age or sex, and analyses suggested that even unvaccinated persons achieved an adequate immune response following a single dose of DS-5670d. There were no major differences in the incidence or severity of adverse events between the study vaccination groups. ConclusionsA single dose of DS-5670d was immunogenically non-inferior to BNT162b2 and acceptably safe in persons with or without a history of prior infection and/or vaccination. Trial RegistrationJapan Registry of Clinical Trials (jRCT2031230424) Author summaryWhy was this study done? O_LIThe global emergency response against the coronavirus disease 2019 (COVID-19) pandemic is now being superseded by annual immunization using an updated vaccine composition to reduce the disease burden associated with newly emerging variants. C_LIO_LIWe conducted a comparative study of two newly authorized updated vaccine compositions containing the antigen derived from omicron XBB.1.5, which was recommended for the 2023/24 season. C_LIO_LIWe intended to assess the immunogenicity and safety of a single dose of DS-5670d compared with BNT162b2 in Japanese adults and children aged [&ge;]12 years. C_LI What did the researchers do and find? O_LIIn persons who had received prior vaccination, or who had previously had COVID-19, or both, DS-5670d was non-inferior to BNT162b2 in terms of blood neutralizing activity and seroresponse rates, and immune responses were not influenced by age or sex. C_LIO_LIAmong unvaccinated persons, those who had been exposed to SARS-CoV-2 by prior infection achieved an adequate immune response following a single dose of DS-5670d; however, the group who had had no previous exposure at all was too small to properly evaluate. C_LIO_LIThere were no major differences in the frequency or severity of adverse events between the study vaccination groups, and there were no DS-5670d-related serious adverse events. C_LI What do these findings mean? O_LIDS-5670d was immunogenically non-inferior to BNT162b2, which has already been widely administered in Japan. C_LIO_LIThere were no new critical safety concerns associated with DS-5670d, suggesting that it could be a useful SARS-CoV-2 vaccine option. C_LIO_LITaken together, the results from this study of DS-5670d and those from previous studies evaluating other compositions of DS-5670, i.e., those containing antigens from different strains of SARS-CoV-2, provide corroborating evidence that the DS-5670 vaccine platform can be applied to produce effective and safe seasonal vaccines against future emerging strains. C_LI

A number of COVID-19 vaccines are under development, with one or more possibly becoming available in 2021. We conducted a global survey in June 2020 of 13,426 people in 19 countries to determine potential acceptance rates of a COVID-19 vaccine and factors influencing acceptance. We ran univariate logistic regressions to examine the associations with demographic variables. 71.5% reported they would be very or somewhat likely to take a COVID-19 vaccine; 61.4% reported they would accept their employers recommendation to take a COVID-19 vaccine. Differences in acceptance across countries ranged from almost 9 in 10 (China) to fewer than 6 in 10 (Russia). Respondents reporting higher levels of trust in information from government sources were more likely to accept a vaccine, and take their employers advice to do so. Targeted interventions addressing age, sex, income, and education level are required to increase and sustain public acceptance of a COVID-19 vaccine.

BackgroundBased on placebo data, it has been recently demonstrated that the frequencies of most common adverse events (AEs) of COVID-19 vaccination are overestimated due to negative expectation bias of vaccine recipients (nocebo effect). Since booster studies lack comparators, estimating the extent of the nocebo effect is difficult. We aimed to overcome this obstacle through a systematic comparison of most common AE frequencies across vaccine doses (first, second, booster), age groups, and vaccine vs. placebo arms. MethodsWe systematically assessed systemic AEs in approved COVID-19 vaccines according to the PRISMA guidelines. All documents regarding COVID-19 vaccines with a booster dose authorized by the FDA (cutoff date 19 November 2021) were systematically searched on PubMed and the FDA website. Solicited systemic AEs from all documents supporting approval/authorization were collected. After standardization of doses and age groups, AE frequencies were compared between vaccine and placebo. FindingsTwo trials were identified for BNT162b2 (n=21,785 participants), two for mRNA-1273 (n=22,324), and one for Ad26.COV2.S (n=4,085). Fever cases dropped to about half with the booster dose in all vaccines, whereas all other systemic AE frequencies were similar to the preceding dose. Almost no fever cases occurred with placebo (first/second dose); all other systemic AEs occurred at high frequencies. After subtracting placebo arm values from vaccine values, the frequencies for the various AEs were roughly comparable within each dose for each vaccine. InterpretationFever is the only solicited systemic AE that can be assessed objectively. It occurs about 50% less often with the booster than with the preceding dose. This may indirectly indicate a considerable overestimation of systemic AEs in the case of booster vaccinations and a pronounced nocebo effect. The nocebo effect appears to substantially contribute to the differences in the frequencies of the various systemic AEs. FundingNo funding received. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA high nocebo effect has recently been shown for the most common solicited adverse events (AEs) based on the randomized controlled trials of several vaccines approved for COVID-19. To date, there has been no systematic review of systemic AEs in COVID-19 vaccines with a booster dose approved by the FDA. Normally, assessing the extent of the nocebo effect requires the implementation of randomized, placebo-controlled studies. However, for ethical reasons, studies underlying the authorization of COVID-19 booster vaccines are not controlled. Therefore, reported AEs lack any reference parameter. We searched PubMed and medRxiv for nocebo effects regarding the objectively measurable AE fever using the terms "(COVID) AND (nocebo) AND (fever)" with no language restrictions; no hits were found on PubMed and six were found on medRxiv. The search without any indication, using only the search terms "(nocebo) AND (fever)", resulted in two hits on PubMed and six hits on medRxiv. An additional search was performed for "(vaccine or COVID) AND nocebo"; 21 hits were found on PubMed and 12 on medRxiv. None of the hits obtained with the three searches showed evidence of relevance for the present topic of a direct association of fever with the nocebo effect. Added value of this studyInstead of placebo AE data as reference parameter, we suggest fever as an objectively measurable value to estimate the extent of the nocebo effect in uncontrolled vaccination studies. To our knowledge, this is a new concept with which evidence for the extent of a possible nocebo effect in COVID-19 booster vaccination can be provided. With this approach we directly supplement information on the most recently reported nocebo effects in first, second and booster vaccine doses. To the best of our knowledge, this is the first study to indirectly compare the solicited systemic AE frequencies of approved COVID-19 vaccines across all doses, with easy-to-understand graphs and based on all approval-relevant trials. This is astonishing, as in the context of a pandemic it is essential to communicate scientific data in a generally understandable manner and according to the highest scientific standards. The graphs provided in this work could serve as an example for such clear communication. Implications of all the available evidenceUsing the example of systemic AEs, we were able to show that the frequency of AEs in COVID-19 booster vaccination may be overestimated. Fever as an objective measure to estimate the nocebo effect could help to optimize public awareness campaigns in the future. The graphic presentation of results facilitates a deeper understanding of complex scientific data and provides new insights. It is therefore ideal for a highly dynamic scientific field and may also be applied to other challenges in the COVID-19 pandemic and beyond.

ObjectivesA randomized, double-blind, active-controlled noninferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPV23). MethodsPneumococcal vaccine-naive participants aged [&ge;]2 years were randomly assigned in a 2:1 ratio to receive a single dose of either the treatment vaccine (n=1199) or a comparator vaccine (n=600). We evaluated the immunogenicity before and 30 days post-vaccination, by measuring serum IgG serotype-specific pneumococcal antibodies to 23 serotypes contained in the vaccines via an enzyme-linked immunosorbent assay. The primary outcome was seroconversion (two-fold increase) of serum IgG serotype-specific antibodies at days 30 compared with baseline. ResultsOne month after the administration of PPV23, seroconversion rates for each of the 23 serotypes ranged from 59.22% to 95.67% in the treatment group, and in the control group from 59.66% to 94.07%. The lower bound of the 95% confidence interval (95%CI) of the rate differences for the 23 serotypes were all larger than -10%. Moreover, 12 serotypes (6B, 23F, 1, 2, 4, 8, 9N, 9V, 11A, 15B, 17F and 18C) had a lower bound of 95%CI for rate difference larger than 0. In total, 236 (19.68%) participants in the treatment group and 118 (19.67%) in the control group reported adverse reactions within 30 days poste-vaccination. No significant differences in incidence of adverse reactions were found between the two comparison groups. ConclusionsThe PPV23 vaccine administered among individual aged [&ge;]2 years was safe, well tolerated and immunogenic, eliciting immune response either comparable to or higher than control vaccine.

BackgroundRising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10g V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. MethodsWe conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10g V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. ResultsThe third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10g V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. ConclusionsA homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

BackgroundThis COVID-19 pandemic has caused unprecedented morbidity, mortality, and global economic instability. Several approved vaccines demonstrated to be effective prevention against COVID-19. We aimed to evaluate the safety and immunogenicity of the PIKA-adjuvanted recombinant SARS-C0V-2 Spike (S) protein subunit vaccine in adults as a primary immunization and as a booster dose against SARS-C0V-2 infection. MethodsThis was a Phase I, open label, dose-escalation study of 3 dose levels of the SARS-CoV-2 spike antigen administered intramuscularly in combination with a fixed dosage of PIKA adjuvant vaccine to evaluate the safety, tolerability, and immunogenicity of PIKA COVID-19 vaccine candidate in healthy adults. The study planned to have 3 arms: Arm A included subjects who had never received any Covid 19 vaccination or have had Covid 19 infection for > 6 months prior to enrolment, Arm B1 included subjects who had completed their primary series of Covid 19 vaccination with an inactivated Covid 19 vaccine and Arm B2 which included subjects whose primary series was completed with mRNA Covid 19 vaccine. The primary safety outcome was adverse events and safety laboratory parameters, and the secondary immunogenicity outcome was neutralizing antibody geometric mean titers and seroconversion rates against the wild type virus, Delta and Omicron variants. This trial is registered with ClinicalTrials.gov, number NCT05305300. FindingsThis interim analysis report presented the results of Arm A and Arm B1 who completed Day 35 for 2 doses in Arm A and Day 28 for a single booster dose in Arm B1. Safety resultsArm A: 60% of participants reported mainly solicited AEs after first and second vaccine. Most of those were local (mainly pain/tenderness) with few systemic (mainly fever and headaches). The majority of participants reported unsolicited events after vaccine which were mainly investigations in hematology/hepatobiliary/Renal or Urine tract infection urine analysis. At least 80% of the participants reported mild AEs. There were 4 SAEs that were mild and were resolved. Also there were 2 medically attended AEs. Arm B1: Less than 50% of the participants reported solicited adverse events which were mainly local (pain and tenderness) and were mild. Also, less than half of the participants reported unsolicited events which were mainly inves-tigations in hematology/hepatobiliary/Renal or Urine tract infection urine analysis. There were no SAE and Medically attended AEs reported. Immunogenicity resultsArm A: The neutralizing antibody GMTs at day 35 were substantially higher than those at baseline for all dose groups and all variants. Seroconversion rates at 35 days ranged between 85.7% and 92.9% for 5g dose group, 92.9% and 100% for the 10g dose group and between 70% and 80% for the high dose group. Arm B1: Similar to Arm A, neutralizing antibody GMTs at day 28 were substantially higher than those at baseline for all dose groups and all variants. Seroconversion rates at 28 days ranged between 92.9% and 100% for 5g dose group, 80% and 100% for the 10g dose group and between 50% and 64.3% for the high dose group. ConclusionThe findings demonstrated that the PIKA Covid 19 vaccine is safe, well tolerated, immunogenic and can be used as a primary vaccination or as a booster dose in participants who had completed an inactivated Covid 19 vaccination series. A comparison of the immune responses presented in this interim analysis showed that geometric mean titer (GMTs) of neutralizing antibody against wild type of SARS-CoV-2 virus, Delta and Omicron of the 5g group was higher than the 10 g and 20 g, therefore the 5g was selected as the recommended dose for the Phase II and III clinical development of the PIKA Covid 19 vaccine.

What is known and objectiveRacial differences in adverse events following COVID-19 vaccines have not been sufficiently studied. Here, we aimed to study the adverse events of Modernas intramuscular COVID-19 vaccine in young Japanese people. MethodsA case-control study was conducted using a questionnaire survey. Risk factors were determined using a multivariable logistic regression model. We also compared the occurrence of systemic adverse events in three pairs (minor and adult; male and female; and occurrence and non-occurrence of adverse events after the first dose). Propensity matching was used to balance variables. ResultsWe analysed 3,369 data points (1,877 after the first dose and 1,492 after the second dose) obtained from a questionnaire survey of 7,965 vaccinated individuals. Comparing the results of the first and second doses, the incidence of local adverse events did not change significantly; however, the incidence of systemic adverse events increased significantly (p < 0.001). Eighty-three percent of the participants complained of local adverse events, and 65% of participants complained of systemic adverse events. Anaphylaxis occurred in one female student (0.03%). Even when an adverse event occurred, most of the symptoms improved within 3 days. Female sex was associated with systemic adverse events after the first and second doses with odds ratios (ORs) (95% confidence interval, CI) of 2.49 (2.03-3.06), and 1.83 (1.28-2.61), respectively. Age (<20 years: minor) was associated with systemic adverse events after the first dose with an OR of 1.80 (1.44-2.24). The results of the analysis of six cohorts that were created using propensity score matching showed that the incidence of systemic adverse events at the first dose in females was significantly higher than that in males, and that of minors was significantly higher than that of adults. What is new and conclusionThe results of this study clarified, for the first time, the risk factors for several adverse events from the injection of Modernas intramuscular COVID-19 vaccine in young Japanese people. This study suggests that women, minors who experienced adverse events after the first dose, those who experienced adverse events after the first dose, and those who had adverse events after the second dose, should be aware of adverse events. What is known and objectiveThe COVID-19 crisis has been spreading worldwide, and the number of infected people is increasing due to the emergence of mutant strains. The COVID-19 vaccine is expected to be effective in preventing coronavirus infection and disease aggravation. In Japan, priority groups, such as healthcare workers and the older adults (aged 65 and over), were the first to be vaccinated. Workplace vaccinations began on 21 June 2021 at universities and businesses; university employees and students have also been vaccinated. In June 2021, in Japan, Modernas intramuscular injection of the COVID-19 vaccine was used for vaccination in places associated with students and corresponding teaching staff. However, as of September 2021, the Comirnaty intramuscular injection vaccine had been used for healthcare workers and elderly people ahead of other COVID-19 vaccines. Adverse events of the Comirnaty intramuscular injection vaccine in healthcare workers and elderly people and that of Modernas intramuscular COVID-19 vaccine in the defence forces, who were prioritised for administration, are currently being studied. However, adverse events associated with the intramuscular injection of Modernas COVID-19 vaccine in young people have not yet been well studied in Japan. 1,2. In addition, racial differences in adverse events following coronavirus vaccines have not been sufficiently studied. We have already reported adverse events associated with the first dose of Modernas intramuscular injection of its COVID-19 vaccine. In Japan, the intramuscular injection of Modernas COVID-19 vaccine will continue to be used in large-scale inoculation venues such as universities and workplaces. Therefore, to clarify the adverse events following coronavirus vaccination in the young Japanese population, we conducted a questionnaire survey after the second dose for students, faculty, and staff who belong to an educational foundation, Kyushu Bunka Gakuen.

BackgroundA recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. MethodsThis was a Phase 2/3 observer-blind, randomized, controlled immuno-bridging study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. ResultsA total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The lower bound of 95% CI of GMT ratios for anti-S IgG GMEUs and neutralizing antibodies in both age groups to those observed in Indian adults were >0.67, thus non-inferiority was met [Anti-S IgG GMT ratios 1.52 (1.38, 1.67), 1.20 (1.08, 1.34) and neutralizing antibodies GMT ratios 1.93 (1.70, 2.18), 1.33 (1.17, 1.50) for 2 to 11 years and 12 to 17 years groups, respectively]. The seroconversion rate was [&ge;] 98% (anti-S IgG) and [&ge;] 97.9 % (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, were the common ([&ge;]5%) solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. ConclusionSII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults. Registration - CTRI No. CTRI/2021/02/031554

IntroductionThis study assessed whether the COVID-19 pandemic has altered parents attitudes toward vaccinating their children against the flu, and the contributing socio-demographic, health-related, and behavioral factors, as well as barriers to school-based vaccination programs. MethodsWe conducted a cross-sectional online survey of parents of children aged 6 months to 11 years in Israel (n=975) between December 21-31, 2022. A multivariate regression was performed to determine predictors of these parents willingness to vaccinate their children aged 6 months to 11 years against the flu in the winter of 2023 (December 2022-February 2023). ResultsOverall, 45% of parents stated that they did not intend to vaccinate their children against the flu in the winter of 2023, citing fears of side effects and concerns about vaccine effectiveness. Among those who did not trust the Ministry of Health and pharmaceutical companies prior to the pandemic, this trend increased in 78% of them following the COVID-19 events. In contrast, 39% of parents stated that they had already vaccinated their children against the flu, with an additional 16% intending to do so. Forty-one percent reported an increased intention following the pandemic. Only 37% of parents vaccinated their children at school in grades 2-4, mainly due to a preference for HMO clinics and lack of available nurses at school. The Health Belief Model (HBM) variables, namely, perceived susceptibility, severity and benefits, displayed the largest effect sizes. ConclusionsUnderstanding the impact of the COVID-19 pandemic on parents willingness to vaccinate their children against the flu is crucial. Notably, the pandemic has increased vaccine receptivity among some parents. Healthcare providers and public health officials need to address parents concerns about the safety and efficacy of the influenza vaccine to improve vaccination rates among children. Implementing school-based vaccination programs is an important strategy for promoting public health, but may be challenging. To increase uptake, nursing staff in student health facilities should be more accessible, and clear explanations about the efficacy of nasal spray vaccinations should be provided.

This paper presents the results of two qualitative surveys in Senegal and in Mali, which include questions about hesitancy to the COVID-19 vaccine between April and June 2021. It took place within a larger 2-year research project involving researchers in Senegal, Mali and Canada which examines the uses of artificial intelligence technologies in the fight against COVID-19. The study involved 1000 respondents in Senegal and 555 in Mali. The researchers found that overall, 55% of respondents in Senegal and 52% of respondents in Mali did not plan to be vaccinated. Hesitancy was much higher in youth aged 15-35 in both cases, with 70% of youth in Senegal and 57% of youth in Mali not planning to be vaccinated, compared to only 42% of elderly in Senegal and 37% of elderly in Mali. The researchers did not find disparities between male and female respondents in Senegal but found some in Mali. They also found that those who had a member of the family with chronic disease (diabetes or hypertension) were slightly more likely to want to be vaccinated. Reasons for vaccine hesitancy fell in several categories, including fear of vaccine side-effects, disbelief in vaccine efficacy or usefulness, and general distrust in the public health system.