Broad-spectrum Delta-BA.2 tandem-fused heterodimer mRNA vaccine delivered by lipopolyplex.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.

Despite mandated primary series, health care personnel still hesitant about COVID-19 vaccine and immunizing children.

IMPORTANCE: Healthcare personnel (HCP) are important messengers for promoting vaccines, for both adults and children. Our investigation describes perceptions of fully vaccinated HCP about COVID-19 vaccine for themselves and primary series for their children. OBJECTIVE: To determine associations between sociodemographic, employment characteristics and perceptions of COVID-19 vaccines among HCP overall and the subset of HCP with children, who were all mandated to receive a COVID-19 vaccine, in a large US metropolitan region. DESIGN: Cross-sectional survey of fully vaccinated HCP from a large integrated health system. SETTING: Participants were electronically enrolled within a multi-site NYS healthcare system from December 21, 2021, to January 21, 2022. PARTICIPANTS: Of 78,000 employees, approximately one-third accessed promotional emails; 6,537 employees started surveys and 4165 completed them. Immunocompromised HCP (self-reported) were excluded. EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): We conducted a survey with measures including demographic variables, employment history, booster status, child vaccination status; vaccine recommendation, confidence, and knowledge. MAIN OUTCOME(S) AND MEASURES: The primary outcome was COVID-19 vaccine hesitancy for all dose types - primary series or booster doses - among HCP. RESULTS: Findings from 4,165 completed surveys indicated that almost 17.2 % of all HCP, including administrative and clinical staff, were hesitant or unsure about receiving a COVID-19 vaccine booster, despite the NYS recommendation to do so. Depending on age group, between 20 % and 40 % of HCP were hesitant about having their children vaccinated for COVID-19, regardless of clinical versus non-clinical duties. In multivariable regression analyses, lack of booster dose, unvaccinated children, females, income less than $50,000, and residence in Manhattan remained significantly associated with vaccine hesitancy. CONCLUSIONS AND RELEVANCE: Despite mandated COVID-19 vaccination, a substantial proportion of HCP remained vaccine hesitant towards adult booster doses and pediatric COVID-19 vaccination. While provider recommendation has been the mainstay of combatting COVID-19 vaccine hesitancy, a gap exists between HCP-despite clinical or administrative status-and the ability to communicate the need for vaccination in a healthcare setting. While previous studies describe the HCP vaccine mandate as a positive force to overcome vaccine hesitancy, we have found that despite a mandate, there is still substantial COVID-19 vaccine hesitancy, misinformation, and reluctance to vaccinate children.

Reliance on sources of immunization information and vaccine uptake among older adults in a rural state: The mediating role of trust.

Older adults are more vulnerable to the negative impacts of infectious diseases than younger individuals. However, regardless of the importance and effectiveness of vaccines to reduce morbidity and mortality, issues remain with vaccine hesitancy among this population. Older adults' sources of immunization information and their level of trust in those sources may play a role in their vaccination behaviors. This research aimed to better understand the role of information sources and related issues of trust as related to vaccine uptake among older adults. A community-based, cross-sectional survey was conducted with 901 older adults in North Dakota in May-July 2022. Measures included extent of reliance on specific sources of immunization information, levels of trust, and uptake for influenza, pneumonia, shingles, and COVID-19 vaccinations. Immunization information sources were grouped into medical experts, informal, and public outlets. Results indicated older adults were more likely to rely on medical experts than informal sources or public outlets for immunization information. Greater reliance on medical experts was associated with a greater likelihood of vaccine uptake for all vaccines, while reliance on public outlets was associated with a greater likelihood of vaccine uptake only for COVID primary series and boosters. Reliance on informal sources for immunization information was associated with a reduced likelihood of vaccine uptake for all vaccines except shingles. Nearly half of respondents were uncertain who to trust for vaccine information. Uncertainty who to trust for immunization information significantly mediated the associations between reliance on medical experts and uptake for most vaccines indicating that trust in medical experts fosters vaccine uptake. Increasing reliance on medical experts as sources of immunization information is vital to increasing vaccine uptake among older adults. Additionally, this population must be assisted in increasing their ability to successfully assess the trustworthiness of immunization information sources.

COVID-19 vaccination perspectives among patients with Long COVID: A qualitative study.

Individuals who have Long COVID may have unique perspectives about COVID-19 vaccination due to the significant impact that COVID-19 has had on their lives. However, little is known about the specific vaccination perspectives among this patient population. The goal of our study was to improve our understanding of perspectives about COVID-19 vaccines among individuals with Long COVID. Interviews were conducted with patients receiving care at a post-COVID recovery clinic. Deductive thematic analysis was used to characterize participant perspectives according to the vaccine acceptance continuum framework, which recognizes a spectrum from vaccine acceptance to refusal. From interviews with 21 patients, we identified perspectives across the continuum of vaccine acceptance. These perspectives included acceptance of vaccines to prevent future illness, concerns about vaccine side effects on Long COVID symptoms, and refusal of vaccines due to perceived natural immunity. A limitation of our study is that these perspectives are specific to individuals receiving care at one post-COVID recovery clinic. In conclusion, our study demonstrates that some patients with Long COVID are uncertain about COVID-19 vaccines and boosters but may also be amenable to conversations that impact future vaccination acceptance. Patient perspectives should be considered when communicating recommendations for COVID-19 vaccinations to this population.

Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

The durability of vaccine-induced protection: an overview.

INTRODUCTION: Current vaccines vary widely in both their efficacy against infection and disease, and the durability of the efficacy. Some vaccines provide practically lifelong protection with a single dose, while others provide only limited protection following annual boosters. What variables make vaccine-induced immune responses last? Can breakthroughs in these factors and technologies help us produce vaccines with better protection and fewer doses? The durability of vaccine-induced protection is now a hot area in vaccinology research, especially after COVID-19 vaccines lost their luster. It has fueled discussion on the eventual utility of existing vaccines to society and bolstered the anti-vaxxer camp. To sustain public trust in vaccines, lasting vaccines must be developed. AREAS COVERED: This review summarizes licensed vaccines' protection. It analyses immunological principles and vaccine and vaccinee parameters that determine longevity of antibodies. The review concludes with challenges and the way forward to improve vaccine durability. EXPERT OPINION: Despite enormous advances, we still lack essential markers and reliable correlates of lasting protection. Most research has focused on humoral immune responses, but we must also focus on innate, mucosal, and cellular responses - their assessment, correlates, determinants, and novel adjuvants. Suitable vaccine designs and platforms for durable immunity must be found.

Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis.

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations.

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Adverse events following immunisation: Prospective cohort study evaluating Australian children presenting to specialist immunisation clinics.

OBJECTIVE: Prior experience of an adverse event following immunisation is a known barrier to vaccination. Limited Australian data evaluating adverse event recurrence among children exists to inform clinical decisions. We aimed to assess adverse event following immunisation recurrence among children with prior adverse events and to evaluate if family history increased adverse event risk. METHODS: A prospective cohort study was conducted from March 3rd until August 18th, 2023. Children ≤ 16 years with prior adverse events following immunisation in themselves or family were recruited from specialist immunisation clinics at two quaternary paediatric hospitals. Adverse event outcomes were collected via surveys administered at presentation, three, and eight days post vaccination, and analysed by key characteristics and potential risk factors. RESULTS: Forty three of forty nine (43/49, 87.8 %) children enrolled received further vaccines. Of those who completed the follow up surveys, 50.0 % (16/32) reported an adverse event. Recurrence of prior adverse events occurred for 23.3 % (10/43, 95 % CI: 11.8 % - 38.6 %) of the cohort. Two of twelve (2/12, 16.7 %) participants with prior serious adverse events who received further vaccines reported a serious adverse event recurrence. No post review serious adverse events were observed in children with prior non serious adverse events. Neurological conditions were a risk factor for prior (neurological condition 3/3 versus no neurological condition 2/40, p < 0.001) and post review (neurological condition 2/3 versus no neurological condition 0/28, p = 0.006) post vaccination seizures. Family history had no relationship to post review adverse events (family history 5/8 versus no family history 11/23, p = 0.685). CONCLUSION: Revaccination is safe for the majority of children with a personal or family history of adverse event following immunisation.

Surname order and revaccination intentions during the COVID-19 pandemic.

Teachers in Japanese schools employ alphabetical surname lists that call students sooner, with surnames appearing early on these lists. We conducted Internet surveys nearly every month from March 2020 to September 2022 with the same participants, wherein we asked participants where the alphabetical columns of their childhood and adult surnames were located. We aimed to identify how surname order is important for the formation of noncognitive skills. During the data collection period, the COVID-19 vaccines became available; Japanese people could receive their third dose starting in December 2021. The 19th wave of the survey was conducted in January 2022. Therefore, to examine how a surname's alphabetical order could influence intention to revaccinate, we used a subsample of data from December 2021 to September 2022. The major findings were as follows. Women with early surnames had an approximately 4% stronger likelihood of having such intentions than men with early surnames. Early name order was more strongly correlated with revaccination intention among women than among men. The surname effect for women was larger when a mixed-gender list was used compared with when it was not used. This effect was only observed for childhood surnames and not for adult surnames.

Modelling the health and economic impacts ofM72/AS01E vaccination and BCG-revaccination: Estimates for South Africa.

BACKGROUND: Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths in 2021. New tuberculosis vaccines could play an important role in reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01E vaccine candidate and BCG-revaccination. The potential population impact of these vaccines is unknown. METHODS: We used an age-stratified transmission model of tuberculosis, calibrated to epidemiological data from South Africa, to estimate the potential health and economic impact of M72/AS01E vaccination and BCG-revaccination. We simulated M72/AS01E vaccination scenarios over the period 2030-2050 and BCG-revaccination scenarios over the period 2025-2050. We explored a range of product characteristics and delivery strategies. We calculated reductions in tuberculosis cases and deaths and costs and cost-effectiveness from health-system and societal perspectives. FINDINGS: M72/AS01E vaccination may have a larger impact than BCG-revaccination, averting approximately 80% more cases and deaths by 2050. Both vaccines were found to be cost-effective or cost saving (compared to no new vaccine) across a range of vaccine characteristics and delivery strategies from both the health system and societal perspective. The impact of M72/AS01E is dependent on the assumed efficacy of the vaccine in uninfected individuals. Extending BCG-revaccination to HIV-infected individuals on ART increased health impact by approximately 15%, but increased health system costs by approximately 70%. INTERPRETATION: Our results show that M72/AS01E vaccination or BCG-revaccination could be cost-effective in South Africa. However, there is considerable uncertainty in the estimated impact and costs due to uncertainty in vaccine characteristics and the choice of delivery strategy. FUNDING: This work was funded by the Bill & Melinda Gates Foundation (INV-001754). This work used the Cirrus UK National Tier-2 HPC Service at EPCC (https://www.cirrus.ac.uk) funded by the University of Edinburgh and EPSRC (EP/P020267/1).

SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase.

It is thought that mRNA-based vaccine-induced immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes quickly, based mostly on short-term studies. Here, we analyzed the kinetics and durability of the humoral responses to SARS-CoV-2 infection and vaccination using >8,000 longitudinal samples collected over a 3-year period in New York City. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state antibody titers than naive individuals. Antibody kinetics were characterized by two phases: an initial rapid decay, followed by a stabilization phase with very slow decay. Booster vaccination equalized the differences in antibody concentration between participants with and without hybrid immunity, but the peak antibody titers decreased with each successive antigen exposure. Breakthrough infections increased antibodies to similar titers as an additional vaccine dose in naive individuals. Our study provides strong evidence that SARS-CoV-2 antibody responses are long lasting, with initial waning followed by stabilization.

Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort study.

BACKGROUND AND AIMS: The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. METHODS: A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses. RESULTS: A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31-3.33) and 8.89 (2.26-35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41-38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53-1.32) and 1.95 (0.53-4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04-0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases. CONCLUSIONS: The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low.

The booster immunization using commercial vaccines effectively protect chickens against novel variants of infectious bursal disease virus (genotype A2dB1).

The novel variant IBDV (nVarIBDV, genotype A2dB1), characterized by bursal atrophy of fabricius and decreased lymphocytes, has been emerging on a large scale in Asia (including China) since late 2018. nVarIBDV is a new threat to the poultry industry, yet the currently licensed commercial vaccines, including the live viral vector vaccine, IBDV immune complex vaccine or VP2 subunit vaccine, are ineffective against nVarIBDV infection. In this study, specific-pathogen-free (SPF) chickens and broilers divided into 3 groups were vaccinated with the live viral vector vaccine, the VP2 subunit vaccine or the IBDV immune complex vaccine at 1 day-old, respectively. The SPF chickens received a secondary vaccination with the live B87 strain vaccine at 11-day-old. The bursa/body weight ratio, histopathology lesion of the bursa, and the differentiation between infected and vaccinated animals (DIVA) by qRT-PCR confirmed that the live viral vector vaccine or immune complex vaccine plus live B87 strain booster could provide at least 80% protection against the FJ2019-01 strain of nVarIBDV in SPF chickens. The broilers also received a secondary vaccination using a live W2512 G-61 strain vaccine at 14-day-old, and analyses showed that the VP2 subunit vaccine or immune complex vaccine plus the live W2512 G-61 strain booster also provided more than 80% protection against the FJ2019-01 strain of nVarIBDV. Unfortunately, the live viral vector vaccine plus live W2512 G-61 strain booster provided poor to moderate protection against FJ2019-01 in broilers. These findings suggest that combining commercial vaccines with rational booster immunization can effectively protect chickens against an nVarIBDV challenge.

Cost-based COVID-19 vaccination and willingness to pay: A post-pandemic review.

The primary objective of this paper is to serve as a valuable resource for policymakers who are confronted with the evolving landscape of the coronavirus disease 2019 (COVID-19), considering both free and cost-based vaccination approaches. The potential consequences of shifting from free to cost-based vaccination are explored, encompassing its impact on global vaccine equity and prioritization, economic well-being, healthcare systems and delivery, public health policies, and vaccine distribution strategies. Examining past studies on willingness to pay for the initial COVID-19 vaccine dose and booster shots provides insights into how individuals value COVID-19 vaccinations and underscores the significance of addressing issues related to affordability. If COVID-19 vaccinations incur expenses, using effective communication strategies that emphasize the importance of vaccination and personal health benefits can increase willingness to pay. Making COVID-19 vaccines accessible through public health programs or health insurance can help alleviate financial barriers and increase vaccination rates.

Low uptake of COVID-19 booster doses among elderly cancer patients in China: A multicentre cross-sectional study.

Background: Vaccination is a crucial measure to control the spread of coronavirus disease 2019 (COVID-19) pandemic. The elderly and cancer populations both are more susceptible to SARS-CoV-2 and have higher mortality. However, the uptake of COVID-19 vaccine booster doses among elderly cancer patients remains unclear. This study aimed to investigate the prevalence and associates of COVID-19 vaccine booster doses uptake in elderly cancer patients. Methods: A multi-center cross-sectional survey was conducted in four general populations of China province from April to June 2022. Demographic and clinical characteristics, as well as COVID-19 vaccination status and reasons for not uptake booster doses, were collected through face-to-face interviews and medical records. Multivariable logistic regression models were performed to explore the associates of the first COVID-19 booster dose vaccination uptake of cancer patients. Results: A total of 893 cancer patients were eventually included in this study, of which 279 (31.24%) were aged 65 or older and 614 (68.76%) were under 65 years old. The proportion of the first COVID-19 vaccine booster dose among cancer patients aged 65 and above was lower than among adults aged 65 (23.66 vs. 31.92%). Factors affecting individual-level variables among the aged 65 and above cancer patients group whether to uptake the first COVID-19 booster dose were negative attitudes toward COVID-19 vaccine booster dose, perceived subjective norm, perceived behavioural control, and other types of chronic disease. There is no significant difference in the incidence of related adverse reactions between the two age groups (P = 0.19). Conclusions: Low uptake of COVID-19 vaccine booster doses among elderly cancer patients is a significant concern and implies high susceptibility and high fatality when facing the emergence of SARS Cov-2 outbreak. Efforts to improve vaccine education and accessibility, particularly in rural areas, may help increase uptake and reduce the spread of SARS-Cov-2.

Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses.

Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.

Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis.

INTRODUCTION: Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received. METHODS: Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria. RESULTS: Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization. CONCLUSIONS: COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

Prototype and BA.5 protein nanoparticle vaccines protect against Omicron BA.5 variant in Syrian hamsters.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with greater transmissibility or immune evasion properties has jeopardized the existing vaccine and antibody-based countermeasures. Here, we evaluated the efficacy of boosting pre-immune hamsters with protein nanoparticle vaccines (Novavax, Inc.) containing recombinant Prototype (Wuhan-1) or BA.5 S proteins against a challenge with the Omicron BA.5 variant of SARS-CoV-2. Serum antibody binding and neutralization titers were quantified before challenge, and viral loads were measured 3 days after challenge. Boosting with Prototype or BA.5 vaccine induced similar antibody binding responses against ancestral Wuhan-1 or BA.5 S proteins, and neutralizing activity of Omicron BA.1 and BA.5 variants. One and three months after vaccine boosting, hamsters were challenged with the Omicron BA.5 variant. Prototype and BA.5 vaccine-boosted hamsters had reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Although no significant differences in virus load were detected between the Prototype and BA.5 vaccine-boosted animals, fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Thus, immunity induced by Prototype or BA.5 S protein nanoparticle vaccine boosting can protect against the Omicron BA.5 variant in the Syrian hamster model. IMPORTANCE: As SARS-CoV-2 continues to evolve, there may be a need to update the vaccines to match the newly emerging variants. Here, we compared the protective efficacy of the updated BA.5 and the original Wuhan-1 COVID-19 vaccine against a challenge with the BA.5 Omicron variant of SARS-CoV-2 in hamsters. Both vaccines induced similar levels of neutralizing antibodies against multiple variants of SARS-CoV-2. One and three months after the final immunization, hamsters were challenged with BA.5. No differences in protection against the BA.5 variant virus were observed between the two vaccines, although fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Together, our data show that both protein nanoparticle vaccines are effective against the BA.5 variant of SARS-CoV-2 but given the increased number of breakthrough infections and continued evolution, it is important to update the COVID-19 vaccine for long-term protection.