Vaccine Exposure Research Articles

Human papillomavirus vaccine to prevent CIN3 or worse (CIN3+): A nationwide case-control study in Japan.

An increase in cervical cancer incidence has been reported in Japan. The Ministry of Health, Labor, and Welfare of Japan has resumed the active recommendation of regular HPV vaccines in 2022. In Japan, the preventive effect of CIN3+ in the real world has not yet been demonstrated in age-adjusted cohort or case-control studies. This study aimed to estimate the effect of the HPV vaccine against CIN3+ in Japanese women. This nationwide case-control study from April 2013 to March 2020 targeted women aged 20-26 years old at the time of cervical screening. We compared HPV vaccination exposure between those with abnormal and those with normal cytology. Abnormal cytology was classified into cervical intraepithelial neoplasia (CIN)1+, CIN2+, and CIN3+. We calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 -OR) × 100. A total of 2790 cases and 13,990 controls (one-to-five matching) were eligible in 37 municipalities in Japan. In this study, 61 CIN3 (2.2%) and 10 squamous cell carcinomas (SCC) (0.4%) were found. The OR for CIN3+ versus controls was 0.14 (95% CI, 0.03-0.75), equating to a vaccine effectiveness of 86%. Of the 10 patients who had SCC none were vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in CIN3+ among women who did versus those who did not receive HPV vaccination.

B-086 Evaluation of Long-Term Adaptive Immune Responses Specific to SARS-CoV-2: Effect of Various Vaccination and Omicron Exposure

Abstract Background The immune response to SARS-CoV-2 becomes increasingly complex as individuals receive different combinations of vaccines and encounter breakthrough infections. Our study aims to describe the immunogenicity observed over a two-year period in healthy individuals who completed two-dose series and then experienced booster and/or Omicron infection. Methods In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center. At 1, 5, 11, and 25 months after second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses using commercially available immunoassays and surrogate virus neutralization tests, along with interferon gamma (IFN-γ)-based enzyme-linked immunosorbent spot (ELIspot) assay using SARS-CoV-2 spike peptide pools. Results As the humoral immune response was monitored longitudinally, robust antibody production persisted after the third antigen exposure, in contrast to the rapid decline observed between the second and third dose injections. All immune metrics tended to increase as the number of vaccine doses increased. We also found a trend toward increased humoral immune response in the homologous mRNA-based vaccine group and enhanced cellular immune response in the vector-based primary series with mRNA booster heterologous combination group. Interestingly, no significant difference was found between Omicron exposure through breakthrough infection and bivalent vaccination. Omicron exposure significantly increased the breadth of neutralizing activity, while it did not significantly alter the cross-reactivity in the cellular immune response. Conclusions We identified individuals with diminished neutralization, aiding decisions for future vaccination prioritization. In addition, our findings suggest the role of cellular immunity as an important correlate of long-term protection through cross-reactivity to emerging variants.

COVID-19 Vaccine Safety in Pregnancy, A Nested Case-Control Study in Births From April 2021 to March 2022, England.

Assessment of COVID-19 vaccine safety in pregnancy using population-based data. Matched case-control study nested in a retrospective cohort. April 2021-March 2022, England. All pregnant individuals aged between 18 and 50 years with valid health records. Individuals identified from the national Maternity Services Data Set (MSDS) had their records linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching included participant's age and estimated week of conception. We compared outcomes across multiple COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for demographic and health characteristics. Adverse pregnancy, maternal and neonatal outcomes. 514 013 individuals were included. We found lower odds of giving birth to a baby who was low birthweight (aOR = 0.86, 95% CI: 0.79-0.93), preterm (aOR = 0.89, 95% CI: 0.85-0.92) or who had an Apgar score < 7 at 5 min of age (aOR = 0.89, 95% CI: 0.80-0.98) for individuals who received at least one dose of COVID-19 vaccine during pregnancy. The odds of admission to intensive care unit during pregnancy were lower in those vaccinated (aOR = 0.85, 95% CI: 0.76-0.95). There was no association between vaccination in pregnancy and stillbirth, neonatal death, perinatal death and maternal venous thromboembolism in pregnancy. COVID-19 vaccines are safe to use in pregnancy. Our findings generated important information to communicate to pregnant individuals and health professionals to support COVID-19 maternal vaccination programmes.

New diagnosis of multiple sclerosis in the setting of recent Sinopharm COVID-19 vaccine (BBIBP-CorV) exposure: A series of clinical cases and updated review of the literature.

Background: Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young individuals. There are limited reports of developing demyelinating events following the coronavirus disease 2019 (COVID-19) vaccination. Methods: We reported all individuals (n = 8) with new MS diagnoses with recent exposure (≤ 6 weeks) to the Sinopharm (BBIBP-CorV) vaccine between September 2021 and June 2022. We also reviewed the related literature published as of September 2023. Results: Of 338 newly diagnosed patients with MS who attended our tertiary referral MS center during the study period, 8 (2.36%) had their first demyelinating attack with a median interval of 2 [2.0, 4.0] weeks following the Sinopharm vaccine (sex ratio 1:1, median age: 20.5 [18.0, 27.0] years). No personal or family history of autoimmune/neurological disorders was documented, except for one patient's history of a previous potential demyelinating event and another's family history of immune thrombocytopenic purpura (ITP). All patients had demyelinating brain MRI lesions, and 4 had cervical spinal cord involvement. The brain areas most commonly affected were the periventricular and subcortical regions. Positive oligoclonal bands (OCBs) in all patients supported the MS diagnosis. All patients were diagnosed with relapsing-remitting MS and received intravenous methylprednisolone (IVMP) alone or in combination with plasma exchange (3/8). Rituximab was the most frequently used disease-modifying treatment (3/8). Conclusion: This study provides preliminary evidence of a potential association between the Sinopharm vaccine and the initial manifestations of MS. However, further larger-scale studies with control groups and long-term follow-ups are needed to confirm this association and determine the underlying mechanisms.

Antibody-mediated control mechanisms of viral infections.

Antibodies generated after vaccination or natural pathogen exposure are essential mediators of protection against many infections. Most studies with viruses have focused on antibody neutralization, in which protection is conferred by the fragment antigen binding region (Fab) through targeting of different steps in the viral lifecycle including attachment, internalization, fusion, and egress. Beyond neutralization, the fragment crystallizable (Fc) region of antibodies can integrate innate and adaptive immune responses by engaging complement components and distinct Fc gamma receptors (FcγR) on different host immune cells. In this review, we discuss recent advances in our understanding of antibody neutralization and Fc effector functions, and the assays used to measure them. Additionally, we describe the contexts in which these mechanisms are associated with protection against viruses and highlight how Fc-FcγR interactions can improve the potency of antibody-based therapies.

Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial.

Studies have reported that repeated annual vaccination may influence influenza vaccination effectiveness in the current season. We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok; Sanofi Pasteur) in adults 18-45 years of age. In the first 2 years, participants were randomized to receive vaccine or saline placebo as follows: placebo-placebo (P-P), placebo-vaccine (P-V), or vaccine-vaccine (V-V). Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of serum samples collected at 5 time points from 95 participants were tested for antibodies against vaccine strains. From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with smaller increases for repeat vaccinees who on average had higher prevaccination titers in year 2. There were statistically significant differences in the proportions of participants achieving ≥4-fold rises in antibody titer for the repeat vaccinees for influenza A(H1N1), B/Victoria, and B/Yamagata, but not for A(H3N2). Among participants who received vaccination in year 2, there were no significant differences between the P-V and V-V groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains. In the first 2 years, during which influenza did not circulate, repeat and first-time vaccinees had similar postvaccination geometric mean titers to all 4 vaccine strains, indicative of similar levels of clinical protection. Clinical Trials Registration. NCT04576377.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following exvivo vaccine exposure. Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that invivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

Trends in Serum Shifts: Unveiling Hyperglycaemia Links PostCOVID-19 Vaccination.

Clinical endocrinology has observed emerging endocrine complications following COVID-19 vaccination, amidst successful reductions in COVID-19 hospitalizations and deaths. The Pfizer-BioNTech and Moderna mRNA vaccines have demonstrated efficacy. Reports indicate a potential association between SARS-CoV-2 vaccination and diabetes, exploring interactions with ACE-2 receptors and molecular mimicry. Additionally, altered liver and kidney function tests post-vaccination prompt investigation into their role in predicting type 2 diabetes. This study aims to explore these biochemical abnormalities in a case-control, single-centre prospective study. This prospective study aimed to evaluate a total of five hundred healthy donors, out of which 203 qualified for final analysis. Participants were selected based on their vaccination status with a COVID-19 vaccine and prior exposure to the SARS-CoV-2 virus. Donors without prior SARS-CoV-2 infection were excluded from the study. Included participants were adults who had received three doses of the COVID-19 vaccine. A total of 203 individuals were included in the study, comprising 104 with type 2 diabetes mellitus (T2DM) and 99 without. Demographic characteristics including age, sex, nationality, Rh factors, ABO blood groups, liver function tests (LFT), kidney function tests (KFT), lactate dehydrogenase (LDH), and mineral ion levels were analysed. Among the participants, the distribution based on HbA1c levels showed 47.8% with HbA1c &#60;7% classified as normal, 38.48% with HbA1c 8-10% classified as high, and 16.64% with HbA1c &#60;10% classified as uncontrolled diabetes. Significant findings included a decrease in magnesium levels to 0.77±0.82 mmol/L (p&#60;0.04*), an increase in LDH levels to 420.70±356.26 µL (p&#60;0.01*), and elevated levels of alkaline phosphatase (143.22 ± 142.62 µL, p&#60;0.001), gamma-glutamyl transferase (GGT) (55.70 ± 32.20 µL, p&#60;0.001), and serum bilirubin (9.23 ± 4.87 µmol/L, p&#60;0.001). Creatinine levels were significantly lower at 116.75 ± 101.94 µmol/L (p#60;0.001), while uric acid levels were significantly elevated at 305.92 ± 145.04 µmol/L (p&#60;0.001) in individuals with uncontrolled HbA1c &#60;10%. A majority of these individuals belonged to the O+ blood group. This study underscores significant shifts in serum biomarkers and their complex interplay with mRNA-based SARS-CoV-2 vaccination and diabetes, particularly in uncontrolled cases. The findings suggest potential autoimmune reactions triggered by the self-adjuvant properties of mRNA and polyethylene glycol lipid conjugates. Variations observed among different blood groups may correspond to racial disparities influencing molecular mimicry mechanisms. Despite these insights, the underlying pathophysiological mechanisms remain unclear, highlighting the critical need for further research to validate and expand upon these findings.

Covid-19 vaccine hesitancy and its predictors among diabetic patients on follow-up at public hospitals in Nekemte Town, Western Ethiopia.

Understanding and addressing the concerns of vaccine-hesitant individuals, including those with chronic diseases, is key to increasing vaccine acceptance and uptake. However, in Ethiopia, there is limited evidence on the COVID-19 vaccine hesitancy and predictor variables among diabetic patients. Hence, the study aimed to assess Covid-19 Vaccine Hesitancy and Predictor variables among Diabetic Patients on Follow-Up at Public Hospitals in Nekemte Town, Western Ethiopia. Facility based cross sectional study was conducted among 422 diabetic patients attending public hospitals at Nekemte Town, Western Ethiopia between January, to February, 2023. Study participants were recruited by systematic random sampling. The data were collected interviewee administered pre-tested structured survey questioner. The collected data were entered and cleaned using Epi-Data software 4.6 version. The cleaned data were analyzed using SPSS. 25.0 Statical software. Descriptive statistics like frequency, mean and percentage, and binary logistic regression was applied to identify independent predictors of Covid-19 vaccine hesitancy and association between variables were declared at p-value of 0.05. The overall magnitude of COVID-19 vaccine hesitancy was 15.2% (95% CI: 11.6-18.7). The top three listed reasons for the COVID-19 vaccine hesitancy were: negative information about the vaccine (32.90%), lack of enough information (21.80%), and vaccine safety concern (19.40%). The hesitancy of the COVID-19 vaccination uptake among diabetes patients was independently influenced by age between 40-49 (Adjusted Odd Ratio [AOR] = 4.52(1.04-19.66)), having vaccine awareness (AOR = 0.029(0.001-0.86)), having a great deal of trust on vaccine development (AOR = 0.028(0.002-0.52)), and a fear amount trust (AOR = 0.05(0.003-0.79)) on the vaccine preparation, vaccinated for COVID-19 (AOR = 0.13(0.04-0.51)), perceived exposure to COVID-19 infection after having the vaccine as strongly agree/agree (AOR = 0.03(0.01-0.17))and neither agree nor disagree (AOR = 0.07(0.02-0.30)). COVID-19 vaccine hesitancy among diabetic patients was relatively low. The identified independent predictors were age, vaccine awareness, COVID-19 vaccination history, awareness on vaccine preparation and exposure status to COVID-19 infection. The relevant agency should focus on efforts to translating these high levels of vaccine acceptance into actual uptake, through targeting identifying predictor variables and vaccine availability for a high-risk diabetes patient.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births

COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.

Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet ahigh burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs. We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources. We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries. The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.

Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines

Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity. In this study, we aimed to explore patterns of T-cell activation after SARS-CoV-2 COVID-19 vaccine exposure in vitro using PBMCs collected from pre-pandemic ChAdOx1 nCoV-19 naïve healthy donors (HDs), and ChAdOx1 nCoV-19 and Pfizer vaccinated controls. PBMCs were assessed for T-cell proliferation using the lymphocyte transformation test (LTT) following exposure to SARS-CoV-2 COVID-19 vaccines. Cytokine analysis was performed via intracellular cytokine staining, ELISpot assay and LEGENDplex immunoassays. T-cell assays performed in pre-pandemic vaccine naïve HDs, revealed widespread lymphocyte stimulation after exposure to ChAdOx1 nCoV-19 (95%), ChAdOx-spike (90%) and the Ad26.COV2. S vaccine, but not on exposure to the BNT162b2 vaccine. ICS analysis demonstrated that CD4+ CD45RO+ memory T-cells are activated by ChAdOx1 nCoV-19 in vaccine naïve HDs. Cytometric immunoassays showed ChAdOx1 nCoV-19 exposure was associated with the release of proinflammatory and cytotoxic molecules, such as IFN-γ, IL-6, perforin, granzyme B and FasL. These studies demonstrate a ubiquitous T-cell response to ChAdOx1 nCoV-19 and Ad26.COV2. S in HDs recruited prior to the SARS-CoV-2 pandemic, with T-cell stimulation also identified in vaccinated controls. This may be due to underlying T-cell cross-reactivity with prevalent human adenoviruses and further study will be needed to identify T-cell epitopes involved.

In vitro mRNA-S maternal vaccination induced altered immune regulation at the maternal-fetal interface.

Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology. This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs). We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs). Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1β remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs. In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Modelling the impact of hybrid immunity on future COVID-19 epidemic waves.

Since the emergence of SARS-CoV-2 (COVID-19), there have been multiple waves of infection and multiple rounds of vaccination rollouts. Both prior infection and vaccination can prevent future infection and reduce severity of outcomes, combining to form hybrid immunity against COVID-19 at the individual and population level. Here, we explore how different combinations of hybrid immunity affect the size and severity of near-future Omicron waves. To investigate the role of hybrid immunity, we use an agent-based model of COVID-19 transmission with waning immunity to simulate outbreaks in populations with varied past attack rates and past vaccine coverages, basing the demographics and past histories on the World Health Organization Western Pacific Region. We find that if the past infection immunity is high but vaccination levels are low, then the secondary outbreak with the same variant can occur within a few months after the first outbreak; meanwhile, high vaccination levels can suppress near-term outbreaks and delay the second wave. Additionally, hybrid immunity has limited impact on future COVID-19 waves with immune-escape variants. Enhanced understanding of the interplay between infection and vaccine exposure can aid anticipation of future epidemic activity due to current and emergent variants, including the likely impact of responsive vaccine interventions.

Lessons Learned on Observed-to-Expected Analysis Using Spontaneous Reports During Mass Vaccination.

During the COVID-19 vaccination campaign, observed-to-expected analysis was used by the European Medicines Agency to contextualise data from spontaneous reports to generate real-time evidence on emerging safety concerns that may impact the benefit-risk profile of COVID-19 vaccines. Observed-to-expected analysis compares the number of cases spontaneously reported for an event of interest after vaccination ('observed') to the 'expected' number of cases anticipated to occur in the same number of individuals had they not been vaccinated. Observed-to-expected analysis is a robust methodology that relies on several assumptions that have been described in regulatory guidelines and scientific literature. The use of observed-to-expected analysis to support the safety monitoring of COVID-19 vaccines has provided valuable insights and lessons on its design and interpretability, which could prove to be beneficial in future analyses. When undertaking an observed-to-expected analysis within the context of safety monitoring, several aspects need attention. In particular, we emphasise the importance of stratified and harmonised data collection both for vaccine exposure and spontaneous reporting data, the need for alignment between coding dictionaries and the crucial role of accurate background incidence rates for adverse events of special interest. While these considerations and recommendations were determined in the context of the COVID-19 mass vaccination setting, they are generalisable in principle.

Evaluation of Long-Term Adaptive Immune Responses Specific to SARS-CoV-2: Effect of Various Vaccination and Omicron Exposure.

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity (p < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays (p < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants (p > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants.

Neutralizing immunity against coronaviruses in Tanzanian health care workers

The ongoing vaccination efforts and exposure to endemic and emerging coronaviruses can shape the population's immunity against this group of viruses. In this study, we investigated neutralizing immunity against endemic and emerging coronaviruses in 200 Tanzanian frontline healthcare workers (HCWs). Despite low vaccination rates (19.5%), we found a high SARS-CoV-2 seroprevalence (94.0%), indicating high exposure in these HCWs. Next, we determined the neutralization capacity of antisera against human coronavirus NL63, and 229E, SARS-CoV-1, MERS-CoV and SARS-CoV-2 (including Omicron subvariants: BA.1, BQ.1.1 and XBB.1.5) using pseudovirus neutralization assay. We observed a broad range of neutralizing activity in HCWs, but no neutralization activity detected against MERS-CoV. We also observed a strong correlation between neutralizing antibody titers for SARS-CoV-2 and SARS-CoV-1, but not between other coronaviruses. Cross-neutralization titers against the newer Omicron subvariants, BQ.1.1 and XBB.1.5, was significantly reduced compared to BA.1 and BA.2 subvariants. On the other hand, the exposed vaccinated HCWs showed relatively higher median cross-neutralization titers against both the newer Omicron subvariants and SARS-CoV-1, but did not reach statistical significance. In summary, our findings suggest a broad range of neutralizing potency against coronaviruses in Tanzanian HCWs with detectable neutralizing immunity against SARS-CoV-1 resulting from SARS-CoV-2 exposure.

Protective role of Bacillus Calmette–Guérin vaccine in Alzheimer's disease progression: A systematic review and meta-analysis

Introduction: Alzheimer's disease (AD) represents a significant societal challenge, highlighting the need to explore effective prevention and treatment approaches. Recent literature has suggested that Bacillus Calmette-Guérin (BCG) vaccine may be a viable therapeutic option for immune disorders associated with AD due to its immunomodulatory properties and protection against various diseases. MethodsThis systematic review aimed to evaluate the association of BCG vaccine in the prevention of AD using six medical-scientific databases. A meta-analytical approach was undertaken to estimate the risk of AD incidence in patients with and without BCG vaccine exposure, followed by subgroup analyses. A risk of bias (RoB) assessment was performed using the Newcastle-Ottawa Scale (NOS). ResultsSix cohort studies meeting our inclusion criteria were included (47,947 participants) in the study. From our meta-analysis, intravesical BCG vaccine administration lowered the risk of incidence of AD by 26% in non-muscle-invasive bladder cancer (p < 0.00001). Subgroup analyses showed that BCG vaccination showed a potentially notable preventive effect on AD in older adults (>75 years) and female participants. Conversely, significant heterogeneity in results was observed among male participants and those aged <75 years. The RoB was low in three studies and unclear in the remaining studies. ConclusionsAlthough our results support the potential benefits of BCG vaccine in preventing AD in specific demographics, we remain cautious about interpreting such results. Further research examining the implications of BCG vaccination for prevention and possible treatment of AD should be undertaken in the future.

Understanding Barriers to Human Papillomavirus Vaccination among Parents of 9-10-Year-Old Adolescents: A Qualitative Analysis.

HPV vaccination rates remain low among US adolescents, with only 54% completing the series in 2019. The vaccine is recommended at age 11-12 but can be given as early as age 9. Although it has been found that offering the vaccine earlier improves completion rates by age 13, parents remain reluctant to allow their younger children to initiate this vaccine. The purpose of this study was to better understand parental beliefs regarding receipt of the HPV vaccine among their children at ages 9-10. A 40 min phone interview was completed with 21 participants who were asked about their vaccine viewpoints. Even after receiving one-on-one education from a patient navigator, many caretakers expressed inadequate knowledge of the HPV vaccine and limited exposure to both positive and negative influences. The biggest concern was vaccine side effects, often resulting from a lack of medical understanding. Most parents were reluctant to vaccinate their children at a school-based clinic or pharmacy and believed that the government should not mandate HPV vaccination for public school attendance. Our study provides insight into parental beliefs and attitudes about HPV vaccination at age 9-10 years and barriers that need to be addressed.