Human Vaccines & Immunotherapeutics

BackgroundThe ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a serious threat to global public health and imposes a severe burden on the entire human population. Faced with a virus that can mutate its structure while immunity is incapacitated, a need to develop a universal vaccine that can boost immunity to coronaviruses is highly needed. DesignFive formulations of two types (CRCx2 and CRCx3) of immune complexes with an immunogen adjuvant were evaluated in a mouse model as candidate SARS CoV-2 vaccines in a pretrial prior to clinical trials in humans. CRCx3 comprises 3 different formulas and CRCx2 comprises 2. Balb/c mice were vaccinated intraperitoneally on days 0/7 with a high or low dose of CRCx2 or on days 0/7/14 with a high, medium, or low dose of CRCx3 series, and their blood was sampled for serum antibody measurements. Mice were challenged with live virus after immunization with either vaccine to evaluate prophylaxis ability or treated with them after challenge to evaluate therapeutic ability on day 15. Immunological markers and histopathological studies as well as titration of neutralizing antibodies to the vaccines were evaluated and analyzed. ResultsCRCx 3 and CRCx 2 vaccine candidates induced elevated levels of positive neutralizing antibodies as well as a cellular immune response with safety, efficient productivity, and good genetic stability for vaccine manufacturing to provide protection against SARS-CoV-2 with relatively higher levels with the high dose CRCx2 candidate combination. ConclusionsHighly efficient protection and therapeutic effect against SARS-CoV-2 were obtained with a double-dose immunization schedule spaced at 7-day intervals using injections 0.25 of or 0.40 ml of CRCx2 vaccine formulations with a 25-mm needle. These results support further evaluation of CRCx in a clinical trial on humans.

BackgroundThe highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of COVID-19 vaccines. MethodsIn the current study, we tested in murine model the immunogenicity of a conventional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal vaccination. The candidate vaccine, CuMVTT-RBD, has been immunologically optimized to incorporate tetanus-toxin and is self-adjuvanted with TLR7/8 ligands. ResultsCuMVTT-RBD elicited strong RBD- and spike- specific systemic IgG and IgA antibody responses of high avidity. Local immune responses were assessed and results demonstrate strong mucosal antibody and plasma cell production in lung tissue. The induced systemic antibodies could efficiently recognize and neutralize different Variants of Concerns of mutated SARS-CoV-2 RBDs. ConclusionIn summary, intranasal vaccination with CuMVTT-RBD shows high immunogenicity and induces protective systemic and local specific antibody response against SARS-CoV-2 and its variants. One sentence summaryEvaluation of an intransal administrated conventional VLP-based vaccine against COVID-19 in a murine model.

In this work we evaluated recombinant receptor binding domain (RBD) based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus Alum, AddaS03, AddaVax or the combination of Alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and Alum as adjuvants have a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus Alum, AddaVax or AddaS03. Antibodies induced with the formulation containing U-Omp19 not only increased their neutralization capacity against the wild-type virus but also cross neutralized alpha, lambda and gamma variants with similar potency. Also, addition of U-Omp19 to vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+Alum formulation induced RBD-specific Th1 and CD8+ T cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal SARS-CoV-2 challenge of K18-hACE2 mice.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against coronavirus disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild type SARS-CoV-2 and from variants B.1.1.7, B.1.351 and P.1 for their immunogenicity and protective effect in vivo against challenge with wild type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7 vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild type SARS-CoV-2 in a mouse model. Author SummaryThe emergence of variants of SARS-CoV-2 has led to an urgency to study whether vaccines will lead to cross-protection against these variants. Here, we demonstrate that vaccination with spike proteins of various variants leads to cross-neutralizing responses, as well as protection in a mouse model against wild type SARS-CoV-2.

COVID-19 pandemic has accelerated the development of vaccines against its etiologic agent, SARS-CoV-2. However, the emergence of new variants of the virus requires new immunization strategies in addition to the current vaccines approved for human administration. In the present report, the immunological and safety evaluation in mice and hamsters of a subunit vaccine based on the RBD sub-domain with two adjuvants of oil origin is described. The RBD protein was expressed in insect cells and purified by chromatography until >95% purity. The protein was shown to have the appropriate folding as determined by ELISA and flow cytometry binding assays to its receptor, as well as by its detection by hamster immune anti-S1 sera under non-reducing conditions. In immunization assays in mice and hamsters, the purified RBD formulated with adjuvants based on oil-water emulsifications and squalene was able to stimulate specific neutralizing antibodies and confirm the secretion of IFN-{gamma} after stimulating spleen cells with the purified RBD. The vaccine candidate was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney. These results demonstrate the potential of the purified RBD administered with adjuvants through an intramuscular route, to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection against infection.

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.

BackgroundData from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901. MethodsIn this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18 to 91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses. ResultsA total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non-inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive. ConclusionResults presented here demonstrate the safe and robust immunogenicity from MVC-COV1901. Previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown. ClinicalTrials.gov registrationNCT05011526

The outbreak of SARS-CoV-2 infections had led to the COVID-19 pandemic which has a significant impact on global public health and the economy. The spike (S) protein of SARS-CoV-2 contains the receptor binding domain (RBD) which binds to human angiotensin-converting enzyme 2 receptor. Numerous RBD-based vaccines have been developed and recently focused on the induction of neutralizing antibodies against the immune evasive Omicron BQ.1.1 and XBB.1.5 subvariants. In this preclinical study, we reported the use of a direct fusion of the type IIb Escherichia coli heat-labile enterotoxin A subunit with SARS CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate. The results showed that intranasal immunization with the RBD-LTA fusion protein in BALB/c mice elicited potent neutralizing antibodies against the Wuhan-Hu-1 and several SARS-CoV-2 variants as well as the production of IgA antibodies in bronchoalveolar lavage fluids (BALFs). Furthermore, the RBD-LTA fusion protein was used as a second-dose booster after bivalent mRNA vaccination. The results showed that the neutralizing antibody titers elicited by the intranasal RBD-LTA booster were similar to the bivalent mRNA booster, but the RBD-specific IgA titers in sera and BALFs significantly increased. Overall, this preclinical study suggests that the RBD-LTA fusion protein could be a promising candidate as a mucosal booster COVID-19 vaccine.

The COVID-19 pandemic is the largest epidemic of the 21st century so far. Over 650 million people have already been infected with the SARS-CoV-2 virus. One of the ways to stop this pandemic, is to vaccinate the population and gain herd immunity. Many different vaccines are being used around the world, with differing efficacy. This review summarizes the 79 publications on the efficacy of the currently existing COVID-19 vaccines. It shows that there are eleven vaccines that have efficacy data published in a PubMed-indexed scientific journal. Most research has been done on the Pfizer/BioNTech BNT162B2 vaccine, and the eleven vaccines generally have a high efficacy in preventing illness. The Pfizer (86%-100%), Moderna (93.2%-94.1%), Sputnik-V (91.6%) and Novavax ([~]90%) vaccines show the highest efficacy, followed by the Sinovac (83.5%), QazCovid-in 82%) and Covaxin (77.8%) vaccines. The Oxford/AstraZeneca (69% - 81.5%) and Johnson & Johnson (66%) vaccines have lower efficacy in preventing illness. This overview also shows efficacies other than in preventing illness (e.g. asymptomatic, severe illness, hospitalization, death) in some cases. The results also show that the vaccines have specific effects on specific age groups (e.g. adolescents, adults, elderly) and people with diseases (e.g. leukemia, other cancers, HIV). Future research in this area will mostly focus on vaccine efficacy on specific strains of the SARS-CoV-2 virus (such as the Omicron variant) as well as the efficacy of booster vaccinations.

We aimed to study the stability of a {beta}-SARS-CoV-2 virus-like particle (VLP) vaccine in a series of preliminary experiments using select stabilising excipients. {beta}-SARS-CoV-2 VLPs were produced and purified using established methodologies. The thermostability of VLPs was tested at 4{degrees}C and -30{degrees}C in the presence or absence of stabilizers polysorbate 80, sorbitol or L-histidine in the presence of a physiological NaCl concentration of 137mM. The integrity of VLPs was assessed using ELISA, Western immunoblot and dynamic light scatter (DLS). {beta}-SARS-CoV-2 VLPs were stable at 4{degrees}C for 14 days and the addition of stabilizing excipients improved stability compared to VLPs in PBS alone. Storage of VLPs at -80{degrees}C maintained particle integrity by DLS analysis for up to 2 years. Excipients helped to maintain the immunogenicity of the VLPs by ELISA and Western immunoblot and DLS analysis revealed that VLPs retained their particulate structure. ImportanceSARS-CoV-2 continues to circulate globally and cause significant illness. The problem of waning immunity to mRNA/LNPs has necessitated frequent boosters to keep pace of emerging variants. The development of alternative vaccines therefore remans a priority. Protein based vaccines, like VLPs, offer a safe alternative able to produce longer lasting immune responses. In this preliminary stability analysis, the {beta}-SARS-CoV-2 VLPs were found to be stable at 4{degrees}C and the addition of excipients improved VLP stability. Storage of VLPs at -30{degrees}C and -80{degrees}C also showed that the VLPs are stable for very long periods. Our findings will be of importance for the ongoing development of a SARS-CoV-2 VLP based vaccine.

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.

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.

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.

Vaccination was a key measure to tackle the Covid-19 pandemic, however adolescents were less likely than adults to accept the vaccine. Low vaccine uptake reduces the effectiveness of vaccination campaigns and threatens global public health. Understanding why adolescents are hesitant to accept new vaccines is therefore crucial to support the development of novel vaccine uptake interventions. Prior reviews have included far fewer citations, excluded qualitative data, studies after 2022 and have not mapped adolescent Covid-19 vaccine behaviour onto psychological models. This systematic review investigated psychological factors influencing attitudes and intentions toward and uptake of Covid-19 vaccines in adolescents aged 10 to 19 years globally. It mapped results onto the COM-B framework to inform future interventions. Our search identified 25,354 citations, and included 77 in this review. The quality of studies was mixed, predominantly cross-sectional in design. According to our review, key influences on adolescent Covid-19 vaccine behaviour were: i) Reflective motivation (safety concerns, perceived susceptibility to/severity of Covid-19, perceived vaccine effectiveness, ii) Social opportunity (social norms, autonomy and prosocial attitudes), iii) Psychological capability (attitude and knowledge about vaccines). Our review provides new insights into psychological factors influencing adolescent Covid-19 vaccine behaviour, and maps factors to the COM-B model of behaviour change. To improve vaccine uptake, future vaccine interventions should support adolescents to think critically about the pros and cons of vaccines and consider external influences on their decisions.

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.

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.

The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.

Studies have shown increased immunogenicity from heterologous boosting. This study specifically assessed boosting with Pfizer-BioNTech in Sputnik V vaccination regimens. Reactogenicity was assessed through adverse events. Immunogenicity was assessed by comparing serum anti-Spike (Anti-S) protein antibody and neutralizing antibody titers before booster administration and after 30 days. A total of 428 participants were recruited in the heterologous arm and 351 in the homologous arm. Adverse events were more frequent in the heterologous arm (p<0.001). No serious adverse events were reported in either arm. Amongst 577 individuals who completed the study, Anti-S antibodies were 14.8 times higher after heterologous boosting, and 3.1 times higher after homologous boosting (p<0.001). Similarly, heterologous boosting showed a 2 fold increase in neutralizing antibodies, compared to a 1.6 fold increase in homologous boosting (p<0.001). In conclusion, both boosting regimens elicited an immunological response, nonetheless heterologous Pfizer-BioNTech showed a higher immunological response, with more adverse effects. ARTICLE SUMMARY LINEBoth homologous and heterologous boosting are effective in eliciting an immunological response, however heterologous boosting with Pfizer-BioNTech elicited a higher immunological response, with more adverse effects.

SARS-CoV-2 is the leading cause of the COVID-19 pandemic that causes acute respiratory syndrome, emerged in late 2019, and was declared a global pandemic on March 11th, 2020. A safe and effective vaccine that prevents SARS-CoV-2 infection or minimize SARS-CoV-2 disease burden is needed. However, in 2021, Low- and middle-income countries (LMICs) face challenges regarding supply of COVID-19 vaccines. Indonesia, as a public sector vaccine manufacturing in developing countries was developed COVID-19 vaccine using a platform based on recombinant subunit proteins, a Receptor Binding Domain (RBD) of SARS-CoV-2 formulated with combination of Alhydrogel and CpG Oligodeoxynucleotides 1018 (CpG). In this study, we report the preclinical study including immunogenicity, toxicity and efficacy of vaccine in animal models. The vaccine immunogenicity tested in mice and non-human primates, the toxicity was done in rodents and non-rodents and challenged study and efficacy was done in non-human primates (NHPs) model. The animal model was vaccinated intramuscularly (IM). The serology result in mice and non-human primates showed significant antibody titers and neutralizing antibody responses compared to the RBD formulations adjuvanted with Alhydrogel only. Safety study in Wistar rats and New Zealand rabbits for single-dose (acute toxicity) and repeated-dose (sub-chronic toxicity) showed no abnormalities in the animals organs and behaviors and no deaths were reported in tested animals. Two doses of vaccination have been shown to protect NHPs against SARS-CoV-2 infection, as detected by drastic viral reduction from sample swab in nasal, anal, trachea and nasal wash in 7 days after virus challenged, also viral load measurement from lung and BAL tissue showed negative result, which gave better result than negative control and control vaccine group. No evidence of disease enhancement was observed. These results support clinical development of SARS-CoV-2 vaccine, and in 2022 this vaccine has been approved for emergency use in Indonesia.

A post-hoc analysis of the phase 2 data was performed for the SARS-COV-2 subunit protein vaccine MVC-COV1901. Anti-spike IgG, neutralization assays with live virus and pseudovirus were used to demonstrate age-dependent vaccine-induced antibody response to the vaccine. Results showed that an association exists between age and immune responses to the vaccine, providing further support for the need of booster shots, especially for the older age groups.