Effective Vaccine Research Articles

Ex-vivo evaluation of Plasmodium falciparum-induced cytokine expression in chronic hepatitis B virus-infected and uninfected individuals

Background Chronic Hepatitis B virus (CHB) infection remains a significant public health problem. Exhaustion of T cells usually contribute to the progression of HBV infection to the chronic state, which can impact the induction of immune responses to other pathogens like Plasmodium falciparum. This, in turn, may affect the effectiveness of malaria vaccines when deployed. This case-control longitudinal study sought to determine how early this T cell exhaustion state establishes, since most of the available data relates to CHB cases that have persisted for much longer times. Methods This longitudinal case-control study compared the expression of 13 cytokines between cases and controls at four time points over one year. These cytokines were induced using whole blood ex-vivo stimulation with three Plasmodium falciparum (3D7 strain) antigens. Results Hepatitis B virus-negative and CHB individuals had comparable levels of TNF-α, IL-1β, IL-6 and IL-10. Interleukin 6 which is important for the elimination of HBV was produced in very high amounts by the two groups. There was no significant difference between the groups in their ability to produce pro-inflammatory cytokines in response to malaria antigens. Conclusion Cytokine responses to the vaccine candidates from both groups were similar, indicating no impairment to the effective immune responses to malaria vaccines and probably parasites in this category of early CHB infected individuals.

Mucosal BCG delivery provides a spectrum of protection from different Mycobacterium tuberculosis strains across susceptible and resistant mouse backgrounds

Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the sole globally licensed vaccine against tuberculosis despite its relatively moderate protection of acute disease through adolescence. We hypothesize that vaccine efficacy from a mucosal BCG vaccination will be directly influenced by Mycobacterium tuberculosis (M.tb) strain and mouse background. Here we investigated the effectiveness of mucosal BCG vaccination via the intranasal route, in resistant and susceptible mouse strains, to protect against laboratory strain H37Rv and clinical strain HN878 M.tb aerosol challenge. We evaluated both pulmonary and disseminated CFU at 4-weeks post-infection in addition to survival endpoints in C57BL/6, SWR, and C3HeB/FeJ mice. Antigen specific T cell responses in the lung post-infection were also evaluated. We observed that in each case intranasal BCG afforded a significant reduction in pulmonary CFU at 4-weeks post-infection compared to matched untreated controls. However, only susceptible mouse strains, SWR and C3HeB/FeJ, demonstrated similarly robust control from bacterial dissemination when CFU in the spleen was evaluated at the same timepoint. In the case of both M.tb H37Rv and M.tb HN878 challenge, intranasal BCG significantly improved survival of each mouse cohort compared to unvaccinated controls. Together these data suggest that there is still much to be learned from the century old vaccine, BCG, and how it drives protection.

Human Papillomavirus (HPV) Vaccination Rates Among U.S. Military Veteran Females and Males and Non-Veterans in the National Health Interview Survey.

Human papillomavirus (HPV) infection is a major risk factor for the development of multiple cancers. Active duty service members have higher rates of HPV infection than civilians, while Veterans are diagnosed with a disproportionately high burden of HPV-associated cancers compared to civilians without prior service. While a highly effective HPV vaccine has been available for over a decade, vaccination rates in the United States remain suboptimal. The objective of this study was to investigate HPV vaccination rates among male and female Veterans compared with their non-Veteran counterparts. We performed a secondary analysis of cross-sectional National Health Interview Survey (NHIS) data pooled from 2015 to 2018 to analyze HPV vaccination rates for respondents aged 18-45 years. We used multivariable logistic regression to compare HPV vaccination rates between Veterans and non-Veterans stratified by sex while controlling for sociodemographic factors, including age, race/ethnicity, education level, income, insurance coverage, and VA coverage. All analyses used NHIS survey weights to produce national estimates. Among 45,493 respondents aged 18 to 45 years, vaccination rates were low across all groups: 9.6% of male Veterans and 8.4% of male non-Veterans (P = .21) had received at least one HPV immunization, whereas 32.0% of female Veterans and 25.1% of female non-Veterans (P = .02) were immunized. After controlling for sociodemographics, both male Veterans (AOR 1.79; 95%CI 1.31, 2.44) and female Veterans (AOR 1.56; 95%CI 1.1, 2.21) exhibited higher odds of HPV vaccination compared to their non-Veteran counterparts. VA coverage was also independently associated with higher odds of HPV vaccination among female Veterans (AOR 2.39; 95%CI 1.10, 5.21). Veterans of both sexes are more likely to be vaccinated than their non-Veteran civilian counterparts. However, vaccination rates overall remain low. To our knowledge, ours is the first study of its kind to establish HPV vaccination rates among female Veterans. These findings underscore the important role of DoD and VA health care systems in improving HPV vaccine uptake and mitigating HPV-associated cancer risk among Veterans.

Communicating about COVID-19 Vaccines: A Qualitative Study on Preferences, attitudes, and Influences on Canadian Post-secondary Student Decisions to Get Vaccinated

Given the reasonably low COVID-19 vaccine rates (e.g., <60% fully vaccinated) among Canadian young adults (18–29), we sought to understand the factors that motivated this demographic to get vaccinated. Fifteen post-secondary students and graduates participated in semi-structured interviews about the type of health information they received during the pandemic, and their communication preferences. Analysis of interview data revealed four themes: (1) Participants had high science and health literacy which equipped them to identify and dismiss misinformation; (2) Participants expressed high trust in official sources which positively impacted their confidence in the vaccines; (3) Participants exhibited a low perceived risk from COVID-19 infection and got vaccinated for reasons beyond personal protection; and, (4) Participants responded best to communication that was targeted and tailored towards them. These themes form a foundation for effective vaccine communication campaigns targeted and tailored toward young adults, which is essential for acceptance of future vaccine recommendations.

Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.

We assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes. We used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models. Among 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days. A third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.

Modeling the population-level impact of a third dose of MMR vaccine on a mumps outbreak at the University of Iowa

Mumps outbreaks among fully vaccinated young adults have raised questions about potential waning of immunity over time and need for a third dose of the measles, mumps, rubella (MMR) vaccine. However, there are currently limited data on real-life effectiveness of the third-dose MMR vaccine in preventing mumps. Here, we used a deterministic compartmental model to infer the effectiveness of the third-dose MMR vaccine in preventing mumps cases by analyzing the mumps outbreak that occurred at the University of Iowa between August 24, 2015, and May 13, 2016. The modeling approach further allowed us to evaluate the population-level impact of vaccination by different timing in relation to the start of the outbreak and varied coverage levels, and to account for potential sources of bias in estimating vaccine effectiveness. We found large uncertainty in vaccine effectiveness estimates; however, our models showed that early introduction of a third dose of MMR vaccine during a mumps outbreak can be effective in preventing transmission. School holidays, such as the winter break, likely played important roles in preventing mumps transmission.

Ultra-rapid detection of nuclear protein of severe fever with thrombocytopenia syndrome virus by colloidal gold immunochromatography assay.

In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie bandavirus (DBV), was first discovered in Henan, China. It is a tick-borne zoonotic virus with a fatality rate ranging from 6% to 30%. Currently, we lack safe and effective vaccines or antiviral drugs to treat SFTSV infection. Therefore, the development of a specific, sensitive, and cost-effective detection method is crucial. Using inactivated SFTSV and recombinant SFTSV nucleocapsid protein (SFTSV-NP), we repeatedly immunized mice with different adjuvants and obtained two monoclonal antibodies against SFTSV-NP, which were used to develop a colloidal gold immunochromatographic assay (ICA) rapid test kit for SFTSV. Compared with nucleic acid testing (gold standard), the ICA test strips are 97.67% accurate in testing clinical serum samples (36 cases of clinical serum samples and seven cases of whole blood samples). The test kit was 100% accurate in detecting different SFTSV strains. No false-positive results were generated when detecting other arboviruses. Therefore, our developed SFTSV test kit conveniently, rapidly, and effectively detects SFTSV.

A stochastic hepatitis B model with media coverage and Lévy noise

Globally, it is evident that vaccination and social media significantly influence the spread of diseases. Research has demonstrated that the spread of diseases can be affected by unforeseen events. Therefore, a stochastic hepatitis B virus (HBV) dynamical model is constructed that incorporates media coverage, while also Lévy noise is included. Itô's formula and the Lyapunov function approach are employed to analyze the existence of a positive global solution. Furthermore, the necessary conditions for disease eradication as well as long-term survival are also established to facilitate the general understanding. The statistics indicate that the media's impact is not immediate and does not lead to disease eradication. To effectively manage the spread of diseases, it is essential to employ a combination of significant noise disruption and a low rate of decline in vaccine effectiveness. Numerical simulations are conducted to demonstrate the analytical findings.

Kaposi Sarcoma as a Possible Cutaneous Adverse Effect of ChAdOx1 nCov-19 Vaccine: A Case Report

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions.

COVID-19 vaccination and lethality reduction: a prospective observational study in Venezuela during the last two waves

BackgroundIn Venezuela, the predominant vaccines administered are BBIBP-CorV and Gam-COVID-Vac. Despite robust evidence from randomized clinical trials validating the effectiveness of COVID-19 vaccines in mitigating hospitalization and mortality, there is still a lack of post-authorization safety studies conducted within this demographic population.MethodsA prospective observational study from October 5, 2021 to March 31, 2022 encompassed COVID-19 vaccinated and unvaccinated patients from four sentinel hospitals in Venezuela. Patient lethality was predicted using Charlson Comorbidity index. Clinical outcomes were assessed through WHO’s COVID-19 Clinical Progression Scale.ResultsOut of the 175 patients assessed, 85 (48.6%) were vaccinated. The median Charlson Comorbidity index was 3 points, with no statistically significant differences observed between the groups (p = 0.2). A total of 50 (28.6%) patients died during the study period, with higher proportion of deaths in unvaccinated patients (35.6% vs. 21.2%, p = 0.035). Advanced age (OR = 1.043, 95% CI = 1.015–1.071, p = 0.002) was associated with increased death risk, whereas vaccination against COVID-19 (OR = 0.428, 95% CI = 0.185–0.99, p = 0.047), high oxygen saturation (OR = 0.964, 95% CI = 0.934–0.995, p = 0.024), and enoxaparin administration (OR = 0.292, 95% CI = 0.093–0.917, p = 0.035) were associated with decreased death risk.ConclusionDuring the third and fourth waves of the pandemic, COVID-19 vaccination was associated with a 57% reduction in lethality among patients in four public hospitals in Venezuela.

Addendum: Effectiveness of mRNA COVID-19 vaccines.

A reader of our article on the 2024-2025 formulations of the mRNA COVID-19 vaccines manufactured by Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax)1 asked us to provide more information on the data that supported their licensure.

Knowledge, Attitudes, and Practices towards Influenza Vaccine among Guangzhou Residents: A Cross-Sectional Study.

Influenza vaccination is an important prevention strategy for flu illness. However, the vaccination rate is still low in Guangzhou, China. This study aimed to understand the status of knowledge, the attitude towards the vaccines' reliability and safety, and other aspects associated with the willingness and practice of influenza vaccines in the pediatric and adult populations of Guangzhou city. This study was performed in eleven districts in Guangzhou between November 2020 and December 2020, including the Yuexiu, Liwan, Haizhu, Tianhe, Baiyun, Panyu, Huadu, Nansha, Huangpu, Zengcheng, and Conghua districts. The parents of children and teenagers under the age of eighteen in Guangzhou were surveyed using self-administered questionnaires in four domains: demographic information, the knowledge status and perception of influenza vaccination, the willingness and attitude towards influenza vaccination, and previous vaccine uptake. A multivariable logistic regression was employed to assess the possible determinants of willingness and practice to receive influenza vaccination, calculating the odds ratios (ORs) and 95% confidence interval (CI). A two-sided p-value < 0.05 was deemed statistically significant. A total of 13,213 valid questionnaires were collected (validity rate 98.8%). Out of these participants, 42.62% (5631 participants) expressed a willingness to receive the influenza vaccine, while 55.40% (7320 participants) reported that their children and teenagers had been vaccinated against the flu. Furthermore, 40.44% of the respondents (5343 participants) or other family members had received the influenza vaccine. Logistic regression indicated that factors such as being female (OR = 1.395, 95% CI: 1.278-1.522), being involved in the work of COVID-19 prevention and control (1.551, 1.396-1.724), affirming the preventive effects of vaccination (2.474, 2.106-2.906), knowing about annual influenza vaccination (2.756, 2.540-2.992), and understanding prioritized influenza vaccination populations (1.464, 1.343-1.596) were all positively associated with vaccination willingness. Conversely, middle-aged persons (aged 40-49 years old) (0.726, 0.617-0.853), higher educational levels (undergraduate versus middle school) (0.858, 0.768-0.959), heightened concerns about vaccine safety (considering side effects are obvious versus considering it is safe and basically no side effects) (0.284, 0.188-0.429) and lower knowledge scores (0.813, 0.701-0.942) were adversely linked with vaccination willingness. These findings provide essential insights for altering the perception of influence and influenza vaccination, as well as enhancing health communication strategies to improve influenza vaccine uptake among Guangzhou residents.

Oswald Avery: Pioneer of Bacterial Vaccines and the First to Discover the Function of DNA.

Dr. Oswald Theodore Avery (1877-1955), M.D., played an immense role in the biological and medical field because of his groundbreaking research. All his life, he worked on Streptococcus pneumoniae, the bacterium that causes pneumonia. He discovered the principle of polysaccharide conjugate vaccines, which now save the lives of millions of children and the elderly.He found that bacteria can transfer plasmids; most importantly, he identified that deoxyribonucleic acid (DNA) is the carrier of genetic information instead of the (at that time widely accepted) protein theory. Though he was never awarded the Nobel Prize, his work was the basis for countless achievementsbuilding on his foundation, ranging from effective vaccines to gene transfer technologies.

Coxiella burnetii Nine Mile phase I primary infection derived protective immunity against C. burnetii reinfection in mice depends on both B and T cells, but T cells play a critical role.

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. Acute Q fever is usually a flu-like, self-limiting or treatable illness, but some infections can turn into a severe and sometimes fatal chronic disease. There is currently no FDA-approved vaccine available for the prevention of human Q fever in the US, development of a safe and effective vaccine for the prevention of human Q fever remains an important goal for public health. However, there is a fundamental gap in knowledge regarding the mechanism of protective immunity against C. burnetii infection. To understand the mechanism of C. burnetii infection induced protective immunity, we examined if C. burnetii Nine Mile phase I (NMI) infection induces protection against C. burnetii reinfection in mice. Our results indicate that NMI-infected mice conferred significant protection against C. burnetii reinfection. We also found that NMI infection derived protection did not depend on the routes of infection and antibodies are required for NMI infection derived protection. In addition, NMI infection elicited a comparable level of protection in Wild type, CD4+ T cell deficient, and CD8+ T cell deficient mice, partial protection in B cell deficient mice but no protection in T cell deficient mice. These results suggest that both B cells and T cells are required for NMI-infection derived protection, but T cells may play a critical role. Therefore, the new generation vaccine for the prevention of human Q fever should be focused on boosting both humoral and T cell immune responses.

Effect of The Pfizer-Biontech Vaccine on Ifn-Γ Serum Levels and its Genetic Variations in Response to Vaccination

Background: Pfizer vaccine, which is a nucleoside-modified mRNA vaccine against coronavirus disease 2019 (COVID-19) is one of the first mRNA products to be approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Aim of the study: The aim of this study is to study the impact of Pfizer vaccine on the levels of interferon gamma (IFN-γ) serum levels and its gene polymorphism after 3 months and 6 months of vaccination with Pfizer vaccine . Materials and methods: This case-control study involved (150) subjects who were divided into three groups (each group included 50 subjects). The first group included (50) vaccinated group 3 months after second dose of Pfizer vaccine, and the second group included (50) vaccinated group 6 month after second dose of Pfizer vaccine. The third group was the control group which included (50) healthy unvaccinated subjects. The study was done during the period from May /2022 to September / 2022). Serum levels of IFN-γ were estimated by ELISA technique. The PCR technique was used to study gene polymorphism for IFN-γ. Results: The results in figure (1) showed that the mean levels of INF-γ among the male participants (after 3 months of vaccination, after 6 months of vaccinations, and the control group) were (292.54, 231.48, and 15.71), respectively, with highly significant differences (HS) between the three groups (p&lt;0.01). The results also showed that the mean levels of INF-γ among female participants (after 3 months of vaccination, after 6 months of vaccinations, and the control group) were (317.31, 228.14, and 15.74), respectively, with highly significant differences (HS) between the three groups (p&lt;0.01). Analysis of rs2430561 SNP of (IFN-γ) gene using Sanger sequencing. Single “T” peak indicative of a T homozygous allele showed that Single “A” peak indicative of a A homozygous allele. Presence of the “T” and “A” peak indicative of T/A heterozygous allele. Conclusion: Pfizer vaccine was shown to have significant impacts on IFN-γ levels and presence of single T/A alleles is indicative of heterogeneous T/A allele on analysis of rs2430561 SNP of (IFN-γ) gene among vaccinated individuals.

VACINAÇÃO CONTRA O HPV EM ADOLESCENTES: BENEFÍCIOS, DESAFIOS E PERSPECTIVAS - UMA REVISÃO SISTEMÁTICA

Introduction: Vaccination against the Human Papillomavirus (HPV) is a fundamental intervention for the prevention of cancers related to the virus, especially cervical cancer. Although recommended by the World Health Organization (WHO) and included in several national immunization programs, adolescent vaccination adherence still faces barriers. This systematic review aims to evaluate the benefits, challenges and prospects of HPV vaccination in adolescents, focusing on studies that address both clinical efficacy and factors influencing vaccine acceptance and coverage. Methodology: A search was conducted in the databases Latin American and Caribbean Literature in Health Sciences (LILACS) and Virtual Library in Health (VHL) to identify studies published between 2018 and 2024. Scientific studies were included that evaluated the effectiveness of vaccination, the perception of parents and adolescents, and public policies to encourage vaccination. Results and discussion: HPV vaccination shows up to 90% effectiveness in preventing infections by oncogenic strains of the virus. However, factors such as misinformation, fear of side effects and cultural resistance were identified as the main challenges for vaccine adherence. The implementation of educational campaigns and the strengthening of public policies aimed at immunization were highlighted as effective strategies to increase vaccination coverage. Conclusion: HPV vaccination in adolescents offers clear benefits in the prevention of virus-related diseases, such as cervical cancer. However, challenges such as low acceptance and misinformation about vaccine safety need to be overcome in order to maximize its effectiveness at the population scale. Coordinated actions between governments, health professionals and communities are needed to increase uptake and ensure broad and effective vaccination coverage.

5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial

WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. The Bill & Melinda Gates Foundation.

Reducing spatial heterogeneity in coverage improves the effectiveness of dog vaccination against rabies.

Vaccination programs are the mainstay of control for many infectious diseases. Heterogeneous coverage is hypothesised to reduce vaccination effectiveness, but this impact has not been quantified in real systems. We address this gap using fine-scale data from two decades of rabies contact tracing and dog vaccination campaigns in Serengeti district, Tanzania. Using generalised linear mixed models, we find that current local (village-level) dog rabies incidence decreases with increasing recent local vaccination coverage. However, current local incidence is most dependent on recent incidence, both locally and in the wider district, consistent with high population connectivity. Removing the masking effects of prior non-local incidence shows that, for the same average prior vaccination coverage beyond the focal village, more spatial variation increases local incidence. These effects led to outbreaks following years when vaccination campaigns missed many villages, whereas when heterogeneity in coverage was reduced, incidence declined to low levels (<0.4 cases/1,000 dogs annually and no human deaths), such that short vaccination lapses thereafter did not lead to resurgence. We inferred ongoing rabies incursions into the district, suggesting regional connectivity as an important source of residual transmission. Overall, we provide an empirical demonstration of how the same average vaccination coverage can lead to differing outcomes based on its spatial distribution, highlighting the importance of fine-scale monitoring in managing vaccination programs.

Effect of EV71 Vaccination on Transmission Dynamics of Hand, Foot, and Mouth Disease and Its Epidemic Prevention Threshold

Objective: To investigate the effect of Enterovirus A71 (EV71) vaccination on the transmissibility of different enterovirus serotypes of hand, foot, and mouth disease (HFMD) in Zhejiang, China. Methods: Daily surveillance data of HFMD and EV71 vaccination from August 2016 to December 2019 were collected. Epidemic periods for each HFMD type were defined, and the time-varying effective reproduction number (Rt) was estimated, which could provide more direct evidence of disease epidemics than case number. General additive models (GAMs) were employed to analyze associations between EV71 vaccination quantity and rate and HFMD transmissibility. The epidemic prevention threshold, represented by required vaccination numbers and rates, was also estimated. Results: Vaccinating every 100,000 children ≤ 5 years could lead to a decrease in the Rt of EV71-associated HFMD by 14.44% (95%CI: 6.76%, 21.42%). Additionally, a positive correlation was observed between vaccinations among children ≤ 5 years old (per 100,000) and the increased transmissibility of other HFMD types (caused by enteroviruses other than EV71 and CA16) at 1.82% (95%CI: 0.80%, 2.84%). It was estimated that an additional 362,381 vaccinations, corresponding to increased vaccine coverage to 54.51% among children ≤ 5 years could effectively prevent EV71 epidemics in Zhejiang. Conclusions: Our findings highlight the importance of enhancing EV71 vaccine coverage for controlling the epidemic of EV71-HFMD and assisting government officials in developing strategies to prevent HFMD.