First Dose Of Vaccine Research Articles

Adherence to the post-exposure prophylaxis among animal bite patients attending rabies clinic at tertiary care hospital – A cross-sectional study

Background: Rabies is an acute and 100% fatal viral disease transmitted to humans through the bite or lick of an infected animal. It can be successfully prevented if a complete course of anti-rabies vaccine (ARV) is taken following an animal bite. The present study reveals the compliance of animal bite victims to post-exposure prophylaxis (PEP). Aims and Objectives: The objectives of the study are as follows:(1) To determine the adherence to PEP among animal bite victims and factors influencing it. Materials and Methods: A retrospective record-based cross-sectional study was conducted at the anti-rabies clinic of VIMS Hospital Ballari. Information regarding sociodemographic variables, animal bite history, category of bite, treatment received, and completion of ARV schedule of all the animal bite cases were collected from the animal bite register and treatment card during the period from July 2023 to December 2023. Results: Out of the total 350 animal bite victims, all of them received the first dose of vaccine, 86.28% completed two doses, 72% completed three doses, and only 51.14% completed the schedule by taking all four doses, 37% of them completed the schedule without any delay, 14% delayed one or more doses, and the rest 49% did not complete the schedule. Conclusion: Adherence to PEP is a dire necessity as rabies is a fatal disease. Counseling the animal bite victims about the importance of adhering to the complete PEP schedule at the time of administering the first dose of vaccine is crucial.

Socio-demographic factors affecting the first and second dose of measles vaccination status among under-five children: Perspectives from South Asian countries

BackgroundThe measles vaccine is crucial in preventing fatalities and reducing widespread childhood infections worldwide, yet achieving the desired immunization rates remains a challenge in developing countries. Our study aims to identify the impact of socio-demographic factors on measles vaccination among children in South Asian countries. MethodsParticipants (89513) were taken from the most recent Demographic and Health Survey (DHS) datasets of South Asian countries between 2015 and 2021. Descriptive statistics and multivariable analyses were employed to find out the factors associated with measles vaccination among South Asian countries. ResultsOur study found that the first dose of vaccinated children was 51.7 % in Afghanistan which is the lowest among South Asian countries. The key determinants related to two doses of measles vaccination include parental characteristics, media access, and antenatal care (ANC). Mothers who had done baby postnatal checkups (AOR = 1.22, CI = 1.17–1.26) and made more than four ANC (AOR = 1.77, CI: 1.65–1.89) were more likely to fully immunize their child than mothers with no postnatal and antenatal checkups. ConclusionThe complete dose of measles vaccination rate in South Asia is still low compared to the first dose of measles vaccination among children. The government and stakeholders should organize frequent awareness programs through media and health personnel to inform people about routine vaccinations to eliminate measles.

The impact of Mpox virus incidence and Mpox virus first-dose vaccination on recent HIV testing.

Understanding the impact of Mpox incidence and Mpox first dose vaccination on recent HIV testing is critical to better address both epidemics. We conducted a regression analysis of Mpox incidence and Mpox first dose vaccinations with recent HIV testing during the 2022 Mpox epidemic. We found that increased Mpox first dose vaccination was associated with a decrease in recent HIV testing in men but not women. Mpox incidence was not associated with changes in HIV testing.

Anti-spike antibody responses to SARS-CoV-2 mRNA vaccines in people with schizophrenia and schizoaffective disorder

ImportanceIndividuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population. ObjectiveTo assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder. DesignThis cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine. SettingA multi-center study including psychiatric healthcare settings in the United States and Europe. Participants205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021. Main outcomes and measuresMean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination. ResultsA total of 205 individuals (mean [SD] age, 44.7 [12.0] years; 90 [43.9%] male) were included, of which 106 (51.7%) were diagnosed with SZ. SZ was associated with lower mean log antibody levels (−0.15; 95% CI, −0.27 to −0.03, P = 0.016) after adjusting for age, sex, body mass index, smoking, days since vaccination, and vaccine manufacturer. In secondary analyses of dose-specific responses, SZ was associated with a lower mean log antibody level after the second dose of vaccine (−0.23; 95% CI -0.39 to −0.06, P = 0.006), but not the first dose of vaccine (0.00; 95% CI -0.18— 0.19, P = 0.96). Conclusions and RelevanceIn this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia.

Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.

The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021. We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination. Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement. Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.

#1635 In hemodialysis patients, COVID-19 vaccination mitigates the variability of clinical and laboratory variables

Abstract Background and Aims Despite prior studies on the clinical impact of COVID-19 and the documented efficacy of COVID-19 vaccinations in hemodialysis (HD) patients, the exact effects of COVID-19 vaccinations on various clinical biomarkers before and after the diagnosis of COVID-19 have not been established. In particular, the longitudinal trajectories of clinical and laboratory parameters remain unknown. We aim to investigate clinical and laboratory variables around the time of COVID-19 diagnosis and how vaccination impacts population trajectories. Method We studied 53,223 HD patients from Fresenius Kidney Care, a large U.S. dialysis organization, who received COVID-19 vaccination between January 1, 2021 and August 2, 2021. Depending on whether or not COVID-19 diagnosis happened after the first dose of vaccination for Johnson & Johnson or after the second dose for all other vaccines, we created two patient cohorts comprising patients infected before (N = 47,443) and after (N = 5780) full vaccination. A nonparametric cubic spline model for flexibility was fitted to the patient data averaged for each day between 60 days before and 60 days after the COVID-19 diagnosis. Clinical parameters include ones that are recorded at each HD treatment (pre-HD temperature, TEMP; pre-HD systolic blood pressure, SBP; pre-HD weight, WT; pre-HD pulse rate, PULSE; intradialytic weight gain, IDWG) and ones that are recorded less frequently (hemoglobin, HGB; white blood cell, WBC; neutrophil-lymphocyte ratio, NLR; platelet count, PLA; albumin, ALB). Results All longitudinal trajectory patterns undergo changes in the days before and after the diagnosis of COVID-19. In both the vaccinated and unvaccinated cohorts, there is an initial increase in TEMP, PULSE, and NLR up to 14 days preceding the diagnosis of COVID-19, followed by a subsequent decrease. Conversely, WT and IDWG exhibit a decline up to 14 days before the diagnosis of COVID-19 and an increase thereafter. ALB maintains a decreasing trend from 14 days prior until 20 days after before increasing again. In the unvaccinated cohort, SBP and WBC start decreasing up to 20 days ahead of diagnosis of COVID-19, whereas the unvaccinated cohort maintains a steady trend, increasing for SBP and decreasing for WBC. The lasting effects of COVID-19 can be found up to 60 days after diagnosis, e.g., WT, PULSE, and HGB. Variations in trend shapes are evident between the vaccinated and unvaccinated cohorts across all variables. Notably, all variables in the vaccinated cohort demonstrate smaller changes around the days of COVID-19 diagnosis. Conclusion We discovered trend changes in multiple variables in the days leading up to COVID-19 diagnosis, corroborating earlier findings. This finding lays the foundation for early detection ahead of regular COVID-19 tests. Prior COVID-19 vaccination mitigates the effect of COVID-19 on several important clinical and laboratory indicators, supporting the need for continued vaccination efforts. Lasting effects from infection are prevalent, extending beyond 60 days after confirmation. Further research is warranted to understand their long-term impact.

Decadal analysis of measles epidemiological data in India (2011–2020)

BackgroundDespite India being one of the largest contributors to the measles burden, crucial epidemiological information is significantly lacking. We have analyzed the national-level representative data between 2011 and 2020 to estimate the national- and state-level incidence, first dose vaccine coverage, and mortality; and developed a prediction model to examine the trend of the disease.MethodsWe extracted the Health Management Information System (HMIS) for monthly aggregated measles cases, deaths, and child immunization (9–11 months) for first dose measles vaccine coverage across all states & Union Territories (UT). Population information & projections were extracted based on Census 2011. A multilevel fixed effect panel data model was used to predict measles incidence rate, assuming measles vaccination coverage as a predictor while accounting for time fixed effects.ResultsTotal 558,536 measles cases and 4209 measles deaths were reported in India between 2010 and 2020. The incidence rate was highest in 2013 (628.8/million population), followed by a significant decline to reach 52.0/million in 2020. Measles vaccination coverage for the first dose was 84.1% in 2011 to 91.3% in 2019. Higher vaccination coverage was significantly correlated (r = 0.7, p = 0.02) with decline of measles incidence rate. The case fatality rate (CFR) was least in 2014 (0.13%) but upsurged consistently reaching to 3.3% in 2020. The predictive model indicates that with a first-dose vaccine coverage of 93.5%, and keeping other factors constant, the national measles incidence is projected to reach zero by 2025.ConclusionMeasles incidence is declining in India due to higher vaccination coverage, yet the rise in death rates emphasizes the need for continued collaborative efforts to achieve a measles-free nation.

Proton pump inhibitors associated with severe COVID-19 among two-dose but not three-dose vaccine recipients.

Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients. This was a territory-wide cohort study of 3272286 vaccine recipients (aged ≥18years) of ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. Among 439154 PS-matched two-dose vaccine recipients (mean age: 65.3years; male: 45.7%) with a median follow-up of 6.8months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188360 PS-matched three-dose vaccine recipients (mean age: 62.5years; male: 49.0%; median follow-up: 9.1months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes. Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.

Adverse effects of COVID-19 vaccines in university students

Background Existing data on adverse effects of coronavirus disease 2019 (COVID-19) vaccines among university students are limited. This study aimed to investigate the characteristics of adverse effects that may arise from administering COVID-19 vaccines to university students in Thailand. Methods An online survey study was conducted among students from 12 Health Sciences faculties, and from 16 non-Health Sciences faculties of two universities from October 2021 to January 2022 to assess types and adverse effects of COVID-19 vaccines received by the students. Results There were 1,439 participating students; 522 (36%) were from Health Sciences faculties, and 917 (64%) were from 16 non-Health Sciences faculties. The types of the first-dose vaccine received were inactivated (49%), viral vector (46%), and mRNA (5%), while the types of the second-dose vaccine received were viral vector (53%), inactivated (40%) and mRNA (7%). The first-dose vaccines’ most common adverse effects of inactivated, viral vector, and mRNA vaccines were muscle pain (47%, 82%, and 58%, respectively). The second-dose vaccines’ most common adverse effects were cough (47%) for inactivated vaccines and muscle pain (49% for viral vector vaccines and 56% for mRNA vaccines). Viral vector vaccines were more likely to cause fever, muscle pain, diarrhoea, headache, and rashes than the others. The mRNA vaccines caused injection site pain more than inactivated vaccines. The majority of adverse effects occurred 24-48 hours after vaccination (68%), were more severe with the first dose compared with the second dose, and resolved spontaneously without any treatment at a hospital. Conclusions The adverse effects experienced by the students were various according to the types and number of doses of COVID-19 vaccines. The adverse effects were mostly non-severe and occurred less for the second dose compared with the first dose.

Breakthrough COVID-19 Infection Among the General Community, Frontline Workers, and Healthcare Workers During the Second and Third Wave in North India: A Longitudinal Study.

Vaccination is among the most important public health tools for preventing the harm caused by communicable diseases. This was particularly true in the case of COVID-19 vaccination during the COVID-19 pandemic. However, no vaccine is 100% effective, and all carry the risk of breakthrough infection in vaccinated individuals. This longitudinal observational study was done on COVID-19-vaccinated individuals at a vaccination site in a tertiary care hospital. The study participants were categorized into the general community, frontline workers, and healthcare workers and were followed up during the study period from June 2021 to May 2022post-vaccination. They were interviewed by telephone regarding adverse effects and breakthrough infections post-vaccination during the second and third wave of the COVID-19 pandemic in India. Incidence of breakthrough infection was calculated in all three categories after they received their first, second, and booster doses of vaccination. Fever was the most common adverse effect among all the categories of participants after the first and second doses. Incidence of breakthrough infection after the second dose of vaccination among frontline workers (RR: 5.7, 95% CI: 0.7-44.2) and healthcare workers (RR: 18.9, 95% CI: 2.6-138.6) was observed to be higher compared to the general community, but no such difference was observed among the three categories after the first dose of vaccination. The incidence of breakthrough infection was found to be the highest in healthcare workers, followed by frontline workers compared to the general community, justifying their work profile and the risk associated with it.

Serum Dehydroepiandrosterone sulfate (DHEA-S) level and its potential impact on immune responses and symptom severity after Oxford-AstraZeneca COVID-19 vaccination

BackgroundDehydroepiandrosterone sulfate (DHEA-S) has been associated with an immunomodulatory function. This study aims to explore the relationship between serum levels of DHEA-S and the immune responses triggered by the Oxford–AstraZeneca COVID-19 vaccine in individuals candidate for vaccination. MethodsSerum levels of DHEA-S, cytokine release, antibody production and virus neutralization potential were assessed in 50 male and 50 female subjects before and 2 weeks after vaccination with Oxford–AstraZeneca COVID-19 vaccine. ResultsLevel of DHEA-S before and 2 weeks after first and second dose of vaccination was not different significantly. Levels of Interleukin (IL)-2 and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum levels of IgM 2 weeks after first dose of vaccination was significantly higher compared to before first dose of vaccination. However, serum levels of IgG 2 weeks after first and second dose of vaccination were significantly higher compared to before first and second dose of vaccination. The 50 % focus reduction neutralization test (FRNT50) titer was significantly higher 2 weeks after both first and second dose of vaccination compared to before vaccination. Levels of DHEA-S did not have significant correlation with levels of IL-2, IFN-γ, IgM and IgG, and FRNT50 before and after first and second dose of vaccination. Vaccination did not result in intense unwanted clinical presentations. ConclusionDHEA-S is not involved in the quality of protective immune response during Oxford-AstraZeneca COVID-19 vaccination.

Effects of astragalus extract, levamisole and ascorbic acid on humoral immunity in chickens vaccinated with newcastle disease vaccines

This study was designed to assess the effects of Astragalus extract, levamisole and ascorbic acid on the humoral immune response of chickens vaccinated with live and inactivated Newcastle Disease (ND) vaccines. Sixty day-old Cobb500 broiler chicks were used for the study. At day old, the maternally derived antibodies (MDA) to ND virus was determined and the chicks were then housed in a bio-secured pen with water and feed given ad-lib. On the sixth day, the MDA decay was determined thereafter, the chicks were shared into 4 treatment groups. Group A (Astragalus extract); Group B (levamisole); Group C (ascorbic acid) and Group D (Control) of 15 chicks each. Response to ND vaccinations was determined through bleeding to obtain sera for haemagglutination inhibition test at 7 and 14 days except for the second booster with inactivated Komarov vaccine where it was done at 7, 14 and 21 days post vaccination respectively. Antibody titres in the chicks 7 days post first dose of vaccination with La Sota was high in all the treatment groups above the control with 100 % of the chicks having protective antibody titre of ≥4 log2 until day 30 when the antibody titres in all the groups dropped drastically following the second dose of live La Sota vaccination as the first booster vaccine. However, following the second booster with inactivated Komarov the antibody titres increased in all the treatment groups in comparison to the control especially in groups B and C with GMTs of 5.8 ± 0.19 log2 and 6.1 ± 0.27 log2 respectively. We observed that ascorbic acid and Levamisole may have humoral immuno-stimulating effects on vaccinated chickens through yet to be fully explored mechanism. It is recommended that ascorbic acid or levamisole could be used during vaccinations as immuno-stimulating agents to enhance humoral antibody response in vaccinated flocks.

Adverse Events Following COVISHIELD and VERO CELL Vaccination Campaigns Against COVID-19.

Vaccination against COVID-19 for Nepalese was initiated in January 2021 for various age groups. People were anxious about receiving the vaccines and were concerned about the safety profile of the vaccine they received. In this study, we have tried to observe the Adverse Events Following Immunization of two different vaccines namely COVISHIELD (ChAdOx1 nCOV-19) and VERO CELL (CZ02 strain), used in different phases of vaccination by the government of Nepal. We conducted a cross-sectional study among people who received COVID-19 vaccines in this study using a self-administered questionnaire. Data was cleaned and then exported to IBM SPSS v.20 for analysis, Chi-square test was used to see the association between different variables and a p-value<0.05 was considered statistically significant. Out of 303 respondents, all had received the first and 270 participants had received the second dose of the COVID-19 vaccine, among which, 133 (43.89%) reported at least one side effect after the first dose of vaccination while 58 (21.48%) had self-reported side effects after the second dose of vaccination. Seventeen percent of the respondents had COVID-19 infection within the past 3 months before receiving COVID-19 vaccine. Three percent of participants had re-infection with COVID-19 after receiving the first or the second dose of the COVID-19 vaccine. Among participants who experienced adverse events, 42% and 62.1% of participants experienced mild adverse events following the first dose and second dose of the vaccine, respectively. Conclusions: The adverse events following immunization for both vaccines after both doses of vaccination were quite low, with 43.89% of participants reporting side effects after the first dose and 21.48% of participants reporting side effects after the second dose. Adverse events were most frequently reported within 24 hours of vaccination and were mostly mild.There was no statistical significance of adverse events between both vaccines.

A Mathematical Modeling of the Vaccination Effect on the SARS-CoV-2 Transmission: Analysis and Simulation

Several illustrative studies on the mathematical modeling and analysis of the Coronavirus have been carried out in a short period of time. There is not enough work that accounts for the vaccination campaign's two stages. In this work, a mathematical model is created to show the impact of the recent two-stage vaccination treatment on the Coronavirus. In the proposed model, five compartments are constructed, namely the susceptible individuals , the first dose of vaccination , the second dose of vaccination , infected and recovered population . The uniqueness, boundedness and existence of the solutions of this model have been discussed. All potential model equilibrium points are determined. The local as well as global stability of the system in terms of the basic reproduction number is investigated. Numerical simulation is also carried out to investigate the influence of parameters affecting the dynamics of the model and to support the gathered analytical findings of the model.

Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics

γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Safety and immunogenicity of CoronaVac in healthy adults: A prospective observational multicenter real-world study in Henan Province, China

ABSTRACT Vaccination has emerged as the primar approach for managing the COVID-19 pandemic. Despite certain clinical trials reporting the safety and immunogenicity of CoronaVac, additional multicenter real-world studies are still necessary. In this study, we recruited 506 healthy volunteers who were not infected with COVID-19 or vaccinated. Each participant provided peripheral blood samples three times: prior to the first dose of vaccine, prior to the second dose, and 8 weeks following the second dose. Ultimately, 388 participants completed the entire follow-up process. No serious adverse events were observed among any of the participants. Within 1 week of vaccination, 13.4% of participants experienced systemic adverse reactions, with fatigue (5.93%) and dizziness (3.35%) being the most frequent. Although some clinical indicators, including creatinine, significantly changed after vaccination (p < 0.05), the mean of all altered indicators remained within the normal range. The positive rates of neutralizing antibodies (NAb), IgG, and IgM were 12.3%, 18.85%, and 5.24% prior to the second dose, respectively; and 57.99%, 86.34%, and 2.32% at 8 weeks following the second dose, respectively. Additionally, seven indicators, such as sex, age, and BMI, were significantly correlated with NAb (p < 0.05). Finally, a prediction model was developed based on age, monocytes, and alanine aminotransferase (ALT) with an AUC value of 87.56% in the train set and 80.71% in the test set. This study demonstrated that safety and immunogenicity of CoronaVac were good. The prediction model based on the baseline clinical characteristics prior to vaccination can help to develop more suitable vaccination strategies.

Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial

Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites. R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.

Can citizenship help analyze the risk of underimmunization in the foreign population?

There is emerging evidence of distrustful attitudes towards vaccination of some sub-populations of migrants in Europe, that are at higher risk for under-immunisation. The Covid-19 pandemic has highlighted health disparities also at a national level: lower levels of Covid-19 vaccine uptake in immigrants' population compared with Italian citizens and a substantial heterogeneity in the first-dose vaccine coverage within immigrants' population have been documented. According to immigrants' citizenship, high coverages were observed in subjects from Southeast Asia and from South-Central America while Eastern Europeans showed the lowest coverages. These data suggest that taking into account immigrants' citizenship can help define appropriate strategies in order to promote a personalized approach to health problems and to strengthen vaccination uptake.

Dynamics of humoral and cellular response to three doses of anti-SARS-CoV-2 BNT162b2 vaccine in patients with hematological malignancies and older subjects.

Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients. To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy. We measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D. An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts. FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.