Reactogenicity Of Vaccines Research Articles

Safety and Effectiveness of the Pfizer-BioNTech COVID-19 Vaccine among Health Staff in Sulaimani City, Iraq: A Prospective Cohort Study

A cohort study was conducted among 210 health staff members in Sulaimani city to assess the safety and effectiveness of the Pfizer-BioNTech vaccine. They were divided into two groups: vaccinated and unvaccinated. The vaccinated group received two doses of the Pfizer vaccine, while the unvaccinated group did not receive any vaccines during this study. Vaccine reactogenicity was assessed using a self-report form. Whereas vaccine immunogenicity was assessed by testing the anti-receptor binding domain IgG (anti-RBD IgG) antibody. Several adverse effects were observed with each dose. The most frequent adverse effects were pain at the inoculation site, tiredness, myalgia and fever. The average adverse effects per person in the first and second doses were 5.3 (SD 3.3) and 6.3 (SD 3.5) respectively (p = 0.005). The immunized group's anti-RBD IgG antibody levels were greatly improved after taking the first and second doses (32.50 and 44.92 binding antibody units (BAU)/mL respectively). After eight months of taking the two doses, the antibody level dropped to 17.00 BAU/mL. This study indicates that the vaccine can be safe and effective for enhancing antibody production.

Reactogenicity of hexavalent vaccines modelled in Swedish birth cohorts.

Reactogenicity of hexavalent vaccines modelled in Swedish birth cohorts.

The Platform trial In COVID-19 vaccine priming and BOOsting (PICOBOO) booster vaccination substudy protocol

BackgroundCoronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended.MethodsThe Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy.DiscussionPICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use.Trial registrationAustralian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0_23112023.

A whole-cell pertussis vaccine engineered to elicit reduced reactogenicity protects baboons against pertussis challenge.

Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423-1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.

Spectrum and Incidence of Adverse Reactions Post Immunization in the Taiwanese Population (2014-2019): An Analysis Using the National Vaccine Injury Compensation Program.

Background: Post-marketing surveillance is crucial for gathering data on vaccine reactogenicity, enhancing public trust in immunization, and promoting vaccine uptake. This study aims to characterize adverse events following immunization (AEFIs) and estimate the incidence rates of adverse reactions (ARs) associated with vaccines included in Taiwan's Expanded Program on Immunization (EPI). This study utilizes data from Taiwan's Vaccine Injury Compensation Program (VICP). Methods: Vaccine injury claims submitted to the VICP between 2014 and 2019 were analyzed. ARs were defined as AEFIs adjudicated as "related" or "indeterminate" by the VICP committee. Data on the annual number of vaccine doses administered were obtained from the Taiwan CDC, which helped calculate the AR incidence rates. Results: A total of 491 AEFI claims were reviewed, with 327 (66.6%) categorized as ARs. The AEFIs were mainly associated with the Bacillus Calmette-Guérin (BCG) vaccine (43.4%) and the seasonal influenza vaccine (22.0%). Most EPI vaccines demonstrated low AR incidence rates, ranging from 1.68 to 13.6 per million doses, with the exception of BCG, which exhibited 162.5 ARs per million doses. Shifting BCG immunization from below 5 months to at least 5 months reduced osteomyelitis incidence significantly, from 41.4 to 7.9 (p = 0.0014), but increased abscess and lymphadenitis cases. Conclusions: EPI vaccines in Taiwan are highly safe, with minimal AR incidences in the general population. The BCG vaccine remains an exception, occasionally causing severe ARs like osteomyelitis. Adjusting the immunization schedule to an older age may mitigate some of these adverse effects.

Molecular mechanisms of Coxiella burnetii formalin-fixed cellular vaccine reactogenicity.

Local and systemic reactogenic responses to Q-VAX have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitized individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reaction sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study, we determined, using depletion and adoptive transfer experiments, that both anti-Coxiella antibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined that whole cell vaccine (WCV) material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy (TEM) of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, because small cell variants (SCVs) are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of large cell variant (LCV). These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti-Coxiella antibodies, CD4+ T cells, and IFNγ each contribute to this process.

The Relationship between Immunogenicity and Reactogenicity of Seasonal Influenza Vaccine Using Different Delivery Methods.

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.

Reactogenicity of Primary Vaccination with Hexavalent Vaccines in Infants: Mathematical Projections in Four Southeast Asian Countries

Reactogenicity of Primary Vaccination with Hexavalent Vaccines in Infants: Mathematical Projections in Four Southeast Asian Countries

Pertussis vaccines, epidemiology and evolution.

Pertussis, which is caused by Bordetella pertussis, has plagued humans for at least 800 years, is highly infectious and can be fatal in the unvaccinated, especially very young infants. Although the rollout of whole-cell pertussis (wP) vaccines in the 1940s and 1950s was associated with a drastic drop in incidence, concerns regarding the reactogenicity of wP vaccines led to the development of a new generation of safer, acellular (aP) vaccines that have been adopted mainly in high-income countries. Over the past 20 years, some countries that boast high aP coverage have experienced a resurgence in pertussis, which has led to substantial debate over the basic immunology, epidemiology and evolutionary biology of the bacterium. Controversy surrounds the duration of natural immunity and vaccine-derived immunity, the ability of vaccines to prevent transmission and severe disease, and the impact of evolution on evading vaccine immunity. Resolving these issues is made challenging by incomplete detection of pertussis cases, the absence of a serological marker of immunity, modest sequencing of the bacterial genome and heterogeneity in diagnostic methods of surveillance. In this Review, we lay out the complexities of contemporary pertussis and, where possible, propose a parsimonious explanation for apparently incongruous observations.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. NCT number: NCT04354480; Clinical Registry number: CR108768.

Comparative structural and immunological analysis of outer membrane proteins and dermonecrotic toxin in Bordetella bronchiseptica canine isolate

Bordetella bronchiseptica is a pathogen causing respiratory infections in mammals. With the improving understanding of companion animals’ welfare, addressing the side effects of bordetella vaccine gains importance in dogs. Studies on diverse subunit vaccines are actively pursued in humans to safely and effectively control bordetellosis. Therefore, our objective was to develop a canine bordetella vaccine inspired by human vaccine development. We evaluated the immunogenicity of the two bacterial components: the outer membrane proteins (OMPs) and the dermonecrotic toxin (DNT) from a canine isolate of B. bronchiseptica. In-silico analysis identified eight domains of DNT, and Domain 3 was selected as the most promising antigen candidate. Additionally, the OMPs were extracted and examined using SDS-PAGE and Western blot analysis. The distinct immunological characteristic of OMPs and DNT-3 were examined individually and in combination. Gene expression and cytokine production were also evaluated in DH82 cells after stimulation with those antigens. Treatment with OMPs resulted in higher level of Th1 related cytokines, while DNT-3 induced a predominant response associated with Th17 and Th2 in the cytokine production. Synergistic effects were observed exclusively on IL-23, indicating increase of a potential risk of side effects when OMPs and DNT act together. These findings provide valuable insights into the reactogenicity of conventional Bordetella vaccines. Further, the presented preclinical data in this study offer an alternative method of the development for an optimal next-generation Bordetella vaccine for companion animals and humans, replacing the acellular vaccines containing both toxin and protein components.

COVID-19 vaccine reactogenicity among participants enrolled in the GENCOV study

BackgroundGENCOV is a prospective, observational cohort study of COVID-19-positive adults. Here, we characterize and compare side effects between COVID-19 vaccines and determine whether reactogenicity is exacerbated by prior SARS-CoV-2 infection. MethodsParticipants were recruited across Ontario, Canada. Participant-reported demographic and COVID-19 vaccination data were collected using a questionnaire. Multivariable logistic regression was performed to assess whether vaccine manufacturer, type, and previous SARS-CoV-2 infection are associated with reactogenicity. ResultsResponses were obtained from n = 554 participants. Tiredness and localized side effects were the most common reactions across vaccine doses. For most participants, side effects occurred and subsided within 1–2 days. Recipients of Moderna mRNA and AstraZeneca vector vaccines reported reactions more frequently compared to recipients of a Pfizer-BioNTech mRNA vaccine. Previous SARS-CoV-2 infection was independently associated with developing side effects. ConclusionsWe provide evidence of relatively mild and short-lived reactions reported by participants who have received approved COVID-19 vaccines.

Development of Mass Spectrometry Imaging on skeletal muscle to characterize the local pro-inflammatory and pro-resolution lipid responses in a vaccination context

Vaccine reactogenicity is well documented at the clinical level but the mechanism involved at the local or systemic level are still poorly understood. Muscular tissue where most vaccines are administered is the first place of interaction between the vaccine formulation and the host's immune cells. So far, this site of vaccine administration is not well documented from a mechanistic standpoint. The study of early molecular events at the injection site is crucial to understand the local response to vaccines. In this paper, we report a standardized workflow, from the injection of vaccine formulations in rabbit muscle, to the analysis by desorption electrospray ionization and histology staining to understand the role of lipids involved in the inflammation and its resolution on striated muscular tissue. The analysis of lipid mediators was optimized at the site of needle insertion to allow the spatial comparison of cellular infiltrates at the injection site. We showed that lipids were distributed across the spatial tissue morphology in a time-dependent manner. The MS imaging applied to vaccinology could pave the way to a better understanding of vaccine reactogenicity and mechanism of action.

A Predictive Model of Vaccine Reactogenicity Using Data from an InVitro Human Innate Immunity Assay System.

A primary concern in vaccine development is safety, particularly avoiding an excessive immune reaction in an otherwise healthy individual. An accurate prediction of vaccine reactogenicity using invitro assays and computational models would facilitate screening and prioritization of novel candidates early in the vaccine development process. Using the modular invitro immune construct model of human innate immunity, PBMCs from 40 healthy donors were treated with 10 different vaccines of varying reactogenicity profiles and then cell culture supernatants were analyzed via flow cytometry and a multichemokine/cytokine assay. Differential response profiles of innate activity and cell viability were observed in the system. In parallel, an extensive adverse event (AE) dataset for the vaccines was assembled from clinical trial data. A novel reactogenicity scoring framework accounting for the frequency and severity of local and systemic AEs was applied to the clinical data, and a machine learning approach was employed to predict the incidence of clinical AEs from the invitro assay data. Biomarker analysis suggested that the relative levels of IL-1B, IL-6, IL-10, and CCL4 have higher predictive importance for AE risk. Predictive models were developed for local reactogenicity, systemic reactogenicity, and specific individual AEs. A forward-validation study was performed with a vaccine not used in model development, Trumenba (meningococcal group B vaccine). The clinically observed Trumenba local and systemic reactogenicity fell on the 26th and 93rd percentiles of the ranges predicted by the respective models. Models predicting specific AEs were less accurate. Our study presents a useful framework for the further development of vaccine reactogenicity predictive models.

Short term Outcomes of COVID-19 Vaccines Among Lactating Mother and Child Dyads in Bangladesh: A Multi-centre, Cross-sectional Study.

The aims of the study are to: (1) determine the short-term reactogenicity of WHO-approved COVID-19 vaccines (i.e., Pfizer-BioNTech, Moderna, Sinovac, Oxford-AstraZeneca, Johnson and Johnson, Covaxin) amongst lactating women and their children, and 2) evaluate lactation-related outcomes following the same vaccines in Bangladesh. This was a multi-centre, self-reported, cross-sectional study of lactating woman-child dyads in Bangladesh. Demographics, past medical history, breastfeeding history and clinical outcomes of lactating woman-child dyads at least 7 days after the last dose of vaccine were determined through a structured questionnaire. There were 750 participants from four centres. The mean age of lactating women and children surveyed were 27.6 (SD ± 4.6) years and 10.3 (SD ± 6.7) months, respectively. Majority (81.2%; 608 of 750) received 2 doses of COVID-19 vaccinations while lactating. Almost all (99.9%; 749 of 750) vaccinated lactating women surveyed reported no change in human milk supply. More than half of the participants (56.9%; 373 of 656) reported no symptoms after both doses of COVID-19 vaccines. There were no serious adverse events such as anaphylaxis or hospital admission. Majority of the lactating women (98.9%; 742 of 750) reported that the children whom they breastfed had no symptoms such as fever or cough. This large study of lactating woman-child dyads in Bangladesh, who received a diverse range of WHO-approved COVID-19 vaccines, showed no serious short-term adverse effects.

Concomitant administration of seasonal influenza and COVID-19 mRNA vaccines

ABSTRACT Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 antigens is unknown. We aimed to understand the impact of mRNA COVID-19 vaccines administered concomitantly on the immune response to influenza vaccines. For this, 128 volunteers were vaccinated during the 22-23 influenza season. Three groups of vaccination were assembled: FLU vaccine only (46, 35%) versus volunteers that received the mRNA bivalent COVID-19 vaccines concomitantly to seasonal influenza vaccines, FluCOVID vaccine in the same arm (42, 33%) or different arm (40, 31%), respectively. Sera and whole blood were obtained the day of vaccination, +7, and +28 days after for antibody and T cells response quantification. As expected, side effects were increased in individuals who received the FluCOVID vaccine as compared to FLU vaccine only based on the known reactogenicity of mRNA vaccines. In general, antibody levels were high at 4 weeks post-vaccination and differences were found only for the H3N2 virus when administered in different arms compared to the other groups at day 28 post-vaccination. Additionally, our data showed that subjects that received the FluCOVID vaccine in different arm tended to have better antibody induction than those receiving FLU vaccines for H3N2 virus in the absence of pre-existing immunity. Furthermore, no notable differences in the influenza-specific cellular immune response were found for any of the vaccination groups. Our data supports the concomitant administration of seasonal influenza and mRNA COVID-19 vaccines.

A Potential Association between Abdominal Obesity and the Efficacy of Humoral Immunity Induced by COVID-19 and by the AZD1222, Convidecia, BNT162b2, Sputnik V, and CoronaVac Vaccines.

Abdominal obesity is highly prevalent in Mexico and has a poor prognosis in terms of the severity of coronavirus disease (COVID-19) and low levels of antibodies induced by infection and vaccination. We evaluated the humoral immune response induced by COVID-19 and five different vaccination schedules in Mexican individuals with abdominal obesity and the effects of other variables. This prospective longitudinal cohort study included 2084 samples from 389 participants. The levels of anti-S1/S2 and anti-RBD IgG antibodies were measured at various time points after vaccination. A high prevalence of hospitalization and oxygen use was observed in individuals with abdominal obesity (AO) who had COVID-19 before vaccination; however, they also had high levels of anti-S1/S2 and anti-RBD-neutralizing IgG antibodies. The same was true for vaccination-induced antibody levels. However, their longevity was low. Interestingly, we did not observe significant differences in vaccine reactogenicity between abdominally obese and abdominally non-obese groups. Finally, individuals with a higher body mass index, older age, and previous COVID-19 had higher levels of antibodies induced by COVID-19 and vaccination. Therefore, it is important to evaluate other immunological and inflammatory factors to better understand the pathogenesis of COVID-19 in the presence of risk factors and to propose effective vaccination schedules for vulnerable populations.

Burden and Impact of Reactogenicity among Adults Receiving COVID-19 Vaccines in the United States and Canada: Results from a Prospective Observational Study.

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study's primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination.

2349. Natural Killer Cells and BNT162b2 mRNA Vaccine Reactogenicity and Durability

Abstract Background Natural killer (NK) cells can both amplify and diminish immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Methods We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores. Results Key observations include: 1) circulating NK cells exhibit an increase in CD56dim CD16- NK cells compared to baseline levels, providing evidence of NK cell activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices compared to individuals with low symptoms scores (195.7 [SD 170.1] vs 118.5 [SD 77.5], p=0.04), and 3) pre-vaccination NK cell numbers were negatively correlated with spike-specific IgG levels six months after two BNT162b2 doses (Rho= -0.14, p=0.043). Conclusion These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses. Disclosures David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID response Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial

Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster

SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, and an mRNA encoding a membrane-anchored RBD. 76 healthy adults aged 18-64y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45μg, N=32), mRNA vaccine (10, 20, or 50μg, N=32), or placebo (saline, N=12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29. govNCT05272605. No vaccine-related serious or medically-attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4+ and CD8+ T cell activation. There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains. Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.