Vaccine Efficacy Data Research Articles

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.

Worldwide variations in COVID-19 vaccination policies and practices in liver transplant settings: results of a multi-society global survey.

Despite the WHO's report of 24 available SARS-CoV-2 vaccines, limited data exist regarding vaccination policies for liver transplant (LT) patients. To address this, we conducted a global multi-society survey (EASL-ESOT-ELITA-ILTS) in LT centers. A digital questionnaire assessing vaccine policies, safety, efficacy, and center data was administered online to LT centers. Out of 168 responding centers, 46.4%, 28%, 13.1%, 10.7%, and 1.8% were from European, American, Western Pacific, Southeast Asian, and Eastern Mediterranean Regions. Most LT centers prioritized COVID-19 vaccine access for LT patients (76%) and healthcare workers (86%), while other categories had lower priority (30%). One-third of responders recommended mRNA vaccine exclusively, while booster doses were widely recommended (81%). One-third conducted post-vaccine liver function tests post COVID-19 vaccine. Only 16% of centers modified immunosuppression, and mycophenolate discontinuation or modification was the main approach. Side effects were seen in 1 in 1,000 vaccinated patients, with thromboembolism, acute rejection, and allergic reaction being the most severe. mRNA showed fewer side effects (-3.1, p = 0.002). COVID-19 vaccines and booster doses were widely used among LT recipients and healthcare workers, without a specific vaccine preference. Preventative immunosuppression adjustment post-vaccination was uncommon. mRNA vaccines demonstrated a favorable safety profile in this population.

Pneumococcal conjugate vaccines in children

Pneumococcal conjugate vaccines (PCVs), which have been in population-wide use in children for over two decades now, are highly efficacious in preventing life threatening pneumococcal infections. The strong herd effect of PCVs through reduction in pneumococcal nasopharyngeal carriage in vaccinated children prevents disease in adults as well. Since 7vPCV, which was the first PCV used widely, several new PCVs with each adding more serotypes have been developed. These new PCVs have been approved using immune-bridging criteria based on an aggregate correlate of protection (Cp) derived from vaccine efficacy and antibody responses data from early PCV trials. This Cp that the World Health Organization (WHO) accepts for assessing new PCVs for which it is impracticable to undertake placebo-controlled trials with clinical outcomes is 0.35 μg mL–1 of enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG). Effectiveness and antibody response data more recently of 13vPCV has led to developing Cp for each individual vaccine serotype, that, for some, varies considerably to 0.35 μg mL–1. In trials of newest PCVs, such as 15vPCV and 20vPCV, the comparator used is 13vPCV that has, in turn, been licensed using immune bridging, which leads to potential ‘downward-drift’ risk of protection from the new PCVs. This and the data that have emerged on serotype replacement disease and dosing schedules makes it important to review and rethink how new PCVs are assessed, their clinical benefits are inferred and vaccination programs are designed.

Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India

BackgroundCervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus...

Vaccination of poultry against highly pathogenic avian influenza - part 1. Available vaccines and vaccination strategies.

Several vaccines have been developed against highly pathogenic avian influenza (HPAI), mostly inactivated whole-virus vaccines for chickens. In the EU, one vaccine is authorised in chickens but is not fully efficacious to stop transmission, highlighting the need for vaccines tailored to diverse poultry species and production types. Off-label use of vaccines is possible, but effectiveness varies. Vaccines are usually injectable, a time-consuming process. Mass-application vaccines outside hatcheries remain rare. First vaccination varies from in-ovo to 6 weeks of age. Data about immunity onset and duration in the target species are often unavailable, despite being key for effective planning. Minimising antigenic distance between vaccines and field strains is essential, requiring rapid updates of vaccines to match circulating strains. Generating harmonised vaccine efficacy data showing vaccine ability to reduce transmission is crucial and this ability should be also assessed in field trials. Planning vaccination requires selecting the most adequate vaccine type and vaccination scheme. Emergency protective vaccination is limited to vaccines that are not restricted by species, age or pre-existing vector-immunity, while preventive vaccination should prioritise achieving the highest protection, especially for the most susceptible species in high-risk transmission areas. Model simulations in France, Italy and The Netherlands revealed that (i) duck and turkey farms are more infectious than chickens, (ii) depopulating infected farms only showed limitations in controlling disease spread, while 1-km ring-culling performed better than or similar to emergency preventive ring-vaccination scenarios, although with the highest number of depopulated farms, (iii) preventive vaccination of the most susceptible species in high-risk transmission areas was the best option to minimise the outbreaks' number and duration, (iv) during outbreaks in such areas, emergency protective vaccination in a 3-km radius was more effective than 1- and 10-km radius. Vaccine efficacy should be monitored and complement other surveillance and preventive efforts.

Statistical Inference for Vaccine Efficacy: A Re-Randomization Procedure to Analyse Poisson Outcomes under Covariate-Adaptive Randomization

Re-randomization inference is used as an alternative approach to more traditional statistical methods. Free from parametric assumptions, its use is particularly suited for studies incorporating covariate-adaptive randomization, and can provide additional evaluation and confirmation of inferences drawn from the original analyses, for example, as a sensitivity analysis. We discuss methodological and computational aspects in the context of a Poisson regression and describe an approach to re-randomization inference. This is tested in a simulation study and then illustrated in a case study in which we evaluate vaccine efficacy data from a previously published influenza vaccine study. Our simulations indicate that re-randomization inference corrects for model misspecification. The case study, which accounted for the minimization factors, shows that the p-value and confidence limits from re-randomization inference agree with the original analysis. In conclusion re-randomization inference is a useful method that can be used to support vaccine clinical development.

Parental Knowledge, Attitudes, and Perceptions Impacting Willingness to Vaccinate Against the Human Papillomavirus in Trinidad.

Background Cervical cancer remains a major cause of morbidity and mortality in young women in Trinidad and Tobago. This study aimed to determine the knowledge, attitudes, perceptions, and beliefs of Trinidadian parents toward human papillomavirus (HPV) vaccination. In addition, factors predictive of willingness to vaccinate were explored. Methodology In this cross-sectional study conducted between March and May 2019, a paper-based survey was self-administered to parents of children in the 5-12-year age group in seven geographically representative Trinidadian primary schools. Results Of the 420 questionnaires distributed, 160 were returned completed (38% response rate). General knowledge that HPV causes cervical cancer and genital warts and is spread by sexual contact was common among 81%, 71%, and 81% of parents, respectively. At least 40% of the respondents expressed uncertainty about the vaccine's long-lasting health problems and its effectiveness in preventing genital warts and cervical cancer. Half of the parents were unsure if the vaccine was harmful. The perceptions that vaccine safety data are fabricated, drug companies cover up the dangers of vaccines, vaccine efficacy data are often fabricated, people are deceived about vaccine efficacy and safety, and conspiracy beliefs were held by 15.5%, 26.1%, 13%, 21.7%, and 28.5% of parents, respectively. There was a negative correlation between knowledge and conspiracy belief scores (ρ = -0.30, p < 0.001). Overall, 45.3% of parents were willing to immunize their children against HPV. Being informed about HPV by a health professional (odds ratio (OR) = 2.9, 95% confidence interval (CI) 1.5-5.8), knowledge of the benefits (OR = 4.6, 95% CI = 2.2-9.6), and a health professional offering the option of vaccination (OR = 3.7, 95% CI = 1.7-8.0) were associated with significantly increased odds of parents willing to vaccinate their child. The agreement that vaccine safety data are often fabricated (OR = 0.31, 95% CI = 0.12-0.84), pharmaceutical companies cover up the dangers of vaccines (OR = 0.14, 95% CI = 0.06-0.37), waiting at the clinic being time-consuming (OR = 0.37, 95% CI = 0.15-0.89), and the beliefs that adolescents are too young to get a vaccine to prevent sexually transmitted disease (OR = 0.16, 95% CI = 0.11-0.83) were associated with a significantly decreased willingness to vaccinate. Conclusions While general knowledge about HPV was high, there remain several areas for parental education regarding the HPV vaccine. Misbeliefs need to be addressed and multilevel interventions are needed to improve HPV vaccine uptake in our setting.

Human papillomavirus vaccine

Cervical cancer is the fourth most common cancer in women worldwide and is a significant public health problem. Currently, there are three bivalent human papillomavirus (HPV) vaccines targeting high-risk HPV types (16, 18), two quadrivalent vaccines targeting two high risk HPV types (16,18) and two low risk types (6,11) and one nonavalent vaccine against HPV 16,18, 31, 33, 45, 52, 58, 6 and 11. All are WHO approved vaccines and show excellent seropositivity (&gt;95%) even at 5–10 years' post-vaccination irrespective of dosing schedule. These vaccines are relatively safe with minor local side effects. The WHO recommends two dosage vaccination schedule for girls aged 9–14 years with an off-label recommendation for a single-dose schedule. HPV vaccination has shown efficacy against the reduction of cervical intraepithelial neoplasia, invasive cervical cancer, anogenital warts and vulvovaginal intraepithelial neoplasia in numerous population/registry-based cohort studies worldwide. Countries such as Australia and Sweden where vaccination began as early as 2006–2008 have seen a major reduction in the incidence of cervical cancer in the vaccinated cohorts. Model based projection studies have also indicated significant vaccine efficacy with two doses and single dose in catch-up programmes. In this article, we provide an update on the vaccine recommendations, immunogenicity and efficacy data derived from registry-based cohort studies and trials published mostly in the last 5 years.

Cost-effectiveness of pneumococcal vaccines among adults aged 65years and older in China: A comparative study.

We aimed to assess the cost-effectiveness and health benefits of 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjunctive vaccine (PCV13), and PCV13-PPSV23 sequential vaccination strategies in preventing pneumonia and other pneumococcal diseases among the senior citizens (≥ 65years) in China. The cost-effectiveness of pneumococcal vaccines compared to no vaccination was estimated using a decision-tree Markov model from a societal perspective. Parameters including epidemiological data, vaccine efficacy and cost data were obtained from previous studies. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were presented as outcomes. Sensitivity analyses were performed to explore the uncertainty in the model. In the base-case analysis, compared with no pneumococcal vaccination, the ICERs of PPSV23, PCV13 and PCV13-PPSV23 are US$10,776.7/QALY, $9,193.2/QALY, and $15,080.0/QALY, respectively. PCV13 is the most cost-effective strategy and the only cost-effective strategy based on a threshold of the one-time national GDP per capita, whereas PPSV23 vaccine strategy is provided with the lowest cost, and PCV13-PPSV23 demonstrates the greatest impact on pneumococcal disease burden. Sensitivity analyses reveal that the results are greatly influenced by serotype coverage, vaccine efficacy, CAP incidence and vaccine prices. The PCV13 vaccination for Chinese seniors is more cost-effective than PPSV23 vaccination and PCV13-PPSV23 sequential vaccination.

COVID-19 vaccine knowledge, attitudes, and experiences of health care workers in Perth, Western Australia: A qualitative study.

Health care workers (HCWs) faced an increased risk of Coronavirus Disease 2019 (COVID-19). Australia's COVID-19 vaccine rollout commenced in February 2021 to priority groups, including HCWs. Given their increased risk, as well as influence on patients' vaccine uptake, it was important that HCWs had a positive COVID-19 vaccination experience, as well as trusting the vaccine safety and efficacy data. Semi-structured interviews were undertaken with 19 public- and privately-practicing HCWs in Western Australia between February-July 2021. Data were deductively analysed using NVivo 12 and guided by the Capability-Opportunity-Motivation-Behaviour model. 15/19 participants had received at least one COVID-19 vaccine. Participants were highly motivated, mostly to protect themselves and to get back to "normal", but also to protect patients. Many had a heightened awareness of COVID-19 severity due hearing from colleagues working in settings more impacted than Western Australia. Participants trusted the COVID-19 vaccine development and approval process; their histories of having to accept vaccines for work helped them to see COVID-19 vaccination as no different. Many recalled initially being unsure of how and when they'd be able to access the vaccine. Once they had this knowledge, half had difficulties with the booking process, and some were unable to access a clinic at a convenient location or time. Participants learnt about COVID-19 vaccination through government resources, health organisations, and their workplace, but few had seen any government campaigns for the wider public. Finally, most had discussed COVID-19 vaccination with their social network. HCWs in Western Australia demonstrated good knowledge about COVID-19 vaccination, with many reasons to vaccinate themselves and support the vaccination of others. Addressing the barriers identified in this study will be important for planning to vaccinate health workforces during future pandemics.

PP140 Economic Evaluation Of Several Vaccination Strategies Against Rotavirus In Spain

IntroductionThe Spanish Ministry of Health asked us about the efficiency of extending the current rotavirus vaccination strategy to all newborns. The current strategy is to vaccinate only to high-risk newborns (premature and those qualified as high-risk by a pediatrician). The objective of this research was to compare three strategies: no-vaccination, vaccination of high-risk newborns and universal vaccination, considering the two vaccines available in Spain: RotaTeq® and Rotarix®.MethodsA cost-utility analysis, based on a de novo Markov model, was carried out both from a societal and a healthcare system perspective. The model follows a cohort of newborns during their life-course. The cycle length is annual and a half-cycle correction was applied. A discount rate of 3 percent was applied in the base case both to costs and utilities. Most of the incidence, probabilities and costs data were Spanish. The Quality Adjusted Life Year (QALY) data were taken from international literature. We assumed a willingness to pay threshold of EUR 25,000 per QALY gained. We performed deterministic one-way sensitivity analysis.ResultsCompared to no-vaccination, the high-risk vaccination strategy is cost-effective assuming the above- mentioned threshold only with Rotarix® from a societal perspective (RotaTeq® EUR 32,008 per QALY; Rotarix® EUR 23,368 per QALY). Universal vaccination is not cost-effective either compared to no-vaccination or compared to the high-risk vaccination strategy and with both perspectives. Vaccine prices and efficacy data are highly sensitive variables. We find that universal vaccination would be cost-effective with a discount of 44.6 and 36.9 percent of the current price of RotaTeq® and Rotarix®, respectively.ConclusionsUniversal vaccination would not be a cost-effective strategy for Spain with either of the two vaccines at current prices. Vaccination of high-risk newborns would be cost-effective at current prices and from a societal perspective only with Rotarix®. Substantial vaccines price reductions could make the universal vaccination a cost-effective option in Spain.

Threshold protective levels of serum IgG to Shigella lipopolysaccharide: re-analysis of Shigella vaccine trials data

ObjectivesEstablishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis. MethodsWe performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei–Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1–4 years in Israel. Adults received either S. sonnei–rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei–rEPA conjugate (n = 1384) or S. flexneri 2a–rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti–S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti–S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels. ResultsAmong adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28–100%). A threshold of ≥1:1600 IgG anti–S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65–80%). The IgG anti–S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3–4 years. The predicted VE in children aged 2–4 years was 49%, consistent with the 52% observed VE. ConclusionSerum IgG anti–S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.

Effectiveness and Cost-Effectiveness of Inactivated Vaccine to Address COVID-19 Pandemic in China: Evidence From Randomized Control Trials and Real-World Studies.

ObjectiveThis study aimed to determine the efficacy, effectiveness, and cost-effectiveness of inactivated COVID-19 vaccines (CoronaVac and BBIBP-CorV) in China using existing international clinical trials and real-world evidence.MethodsThrough a search of PubMed, Embase, Web of Science, and CNKI, studies investigating the effectiveness of inactivated COVID-19 vaccines were identified, and a meta-analysis was undertaken to synthesize the vaccine efficacy and effectiveness data. Moreover, a decision-analytic model was developed to estimate the cost-effectiveness of inactivated vaccines for combating the COVID-19 pandemic in the Chinese context from a societal perspective. Results of the meta-analysis, along with cost data from official websites and works of literature were used to populate the model. Sensitivity analysis was performed to test the robustness of the model results.ResultsA total of 24 studies were included in the meta-analysis. In comparison to no immunization, the effectiveness of inactivated vaccine against COVID-19 infection, hospitalization, ICU admission and death were 65.18% (95% CI 62.62, 67.75), 79.10% (95% CI 71.69, 86.51), 90.46% (95% CI 89.42, 91.50), and 86.69% (95% CI 85.68, 87.70); and the efficacy against COVID-19 infection and hospitalization were 70.56% (95% CI 57.87, 83.24) and 100% (95% CI 61.72, 100). Inactivated vaccine vaccination prevented more infections, hospitalizations, ICU admissions, and deaths with lower total costs, thus was cost-saving from a societal perspective in China. Base-case analysis results were robust in the one-way sensitivity analysis, and the percentage of ICU admission or death and direct medical cost ranked the top influential factors in our models. In the probabilistic sensitivity analysis, vaccination had a 100% probability of being cost-effective.ConclusionInactivated vaccine is effective in preventing COVID-19 infection, hospitalization, ICU admission and avoiding COVID-19 related death, and COVID-19 vaccination program is cost-saving from societal perspective in China.

COVID-19 vaccine perceptions among South Asian communities in the UK: An application of the theory of planned behavior.

Based on the Theory of Planned Behavior, this paper explores the perceptions of the COVID-19 vaccine among South Asian communities residing in the UK. Thirty-eight semi-structured interviews were conducted using a qualitative approach and analyzed using thematic analysis. Participants represented Indian, Pakistani, Bangladeshi, Sri Lankan, Afghani, and Nepali backgrounds. The participants revealed that family and community influence their perceptions of the COVID-19 vaccine. The results suggest that normalizing vaccine acceptance, addressing unknown side effects, and popularizing vaccine efficacy data will increase vaccine uptake within the South Asian community in the UK.

Rapid evaluation of COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 variants by analysis of genetic distance

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7–96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.

Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States-January-July, 2021.

As of March 2021, three COVID-19 vaccines had been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic COVID-19 cases among vaccinated people (vaccine breakthrough infections) based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 199,000 symptomatic vaccine breakthrough infections (95% CI: ~183,000–214,000 cases) occurred in the United States during January–July 2021 among >156 million fully vaccinated people. With high SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.

A qualitative insight into the perceptions and COVID-19 vaccine hesitancy among Pakistani pharmacists

ABSTRACT A qualitative exploration of pharmacists’ perceptions regarding COVID-19 conspiracies and their willingness to get vaccinated. A semi-structured questionnaire guide was developed using ground theory to conduct in-depth interviews. A total of 36 participants gave consent for an audio-recorded interview. Results have shown that most of the respondents believed that SARS-CoV-2 is a natural virus, not man-made, that causes a disease just like other viruses and it is absurd to believe that the vaccine is being used by foreign powers for the implantation of microchips just to control humans. A general opinion thatwhich reflected from the in-depth interview is that the pharmaceutical companies may be hiding some important information on COVID-19 to promote the sale of their product. Some doubts on the reliability and trustworthiness on the COVID-19 vaccine safety and efficacy data were noticed among the respondents. Factors leading to COVID-19 vaccine hesitancy were adverse reaction, cost of COVID-19 vaccine, and limited data on safety and efficacy profile of COVID-19 vaccine. COVID-19 vaccine hesitancy among health professionals is a major hindrance to our current fight against COVID-19 pandemic. Findings of this study are alarming, and the stakeholders must consider this ongoing vaccination campaign as an opportunity to formulate a mechanism to ensure high vaccination rate among general public and healthcare providers in Pakistan. KEY POINTS What was already known? According to World Health Organization (WHO), vaccine hesitancy is one of the ten major threats to global healthcare system and it is a major barrier to achieve herd immunity around the globe. Pakistan has begun vaccinating its people in a systematic phase-wise manner under which the healthcare workers and elderly people are prioritized for vaccination. Previous experience tells us that vaccine hesitancy is a major problem in Pakistan and it is better to understand perceptions of pharmacists about COVID-19 vaccine who are the primary source of information for most of general population. What this study adds: This study is first of its kind to explore vaccine hesitancy among Pakistani pharmacists and the results of this study show that majority of the participants were willing to get COVID-19 vaccine and few of them have even got themselves vaccinated at the start of vaccination campaign. Many among the willing participants considered cost of vaccine, adverse reactions, limited data, safety, and efficacy as major hindrance to their decision to get vaccine. Few participants were found highly vaccine-hesitant because of their staunch belief in the prevalent myths and rumors about COVID-19 vaccine.

Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ Tcell responses.

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%–76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection.

Assessing the risk of vaccine-driven virulence evolution in SARS-CoV-2.

The evolution of SARS-CoV-2 virulence, or lethality, threatens to exacerbate the burden of COVID-19 on society. How might COVID-19 vaccines alter selection for increased SARS-CoV-2 virulence? Framing current evidence surrounding SARS-CoV-2 biology and COVID-19 vaccines in the context of evolutionary theory indicates that prospects for virulence evolution remain uncertain. However, differential effects of vaccinal immunity on transmission and disease severity between respiratory compartments could select for increased virulence. To bound expectations for this outcome, we analyse an evo-epidemiological model. Synthesizing model predictions with vaccine efficacy data, we conclude that while vaccine-driven virulence remains a theoretical possibility, the risk is low if vaccines provide sustained robust protection against infection. Furthermore, we found that any increases in transmission concomitant with increases in virulence would be unlikely to threaten prospects for herd immunity in a highly immunized population. Given that virulence evolution would nevertheless impact unvaccinated individuals and populations with low vaccination rates, it is important to achieve high vaccination rates worldwide and ensure that vaccinal immunity provides robust protection against both infection and disease, potentially through the use of booster doses.

How many lives do COVID vaccines save? Evidence from Israel

BackgroundIsrael began a mass vaccination program with the rapid rollout of the Pfizer-BioNTech COVID-19 BNT162b2 vaccine for adults. At the same time, government stringency measures in terms of closing public life were decreased. Our objective was to estimate the total number of Covid-19 deaths avoided due to the massive vaccination campaign in the elderly Israeli population.MethodsWe examined the effect of vaccination on mortality when at least 90% of the population over age 70 were vaccinated for less than seven months. Projected deaths as expected from vaccine efficacy and actual mortality data were compared for the study population to account for potential confounding effects of government stringency. The average Oxford Stringency Index was calculated in the study period and the preceding period of the pandemic. Potential confounding effects of an age shift in the distribution of deaths were examined by analyzing the distributions before and after the study period.ResultsConfirmed deaths from COVID-19 in the population over 70 after mass vaccination were recorded as 370, versus 5,120 estimated without vaccinations.ConclusionsVaccines against COVID-19 saved more lives than expected by simply applying individual vaccine efficacy to the vaccinated population in Israel, despite a loosening of government stringency. Our findings support the worldwide efforts of governments to improve vaccination rates, especially in the elderly population.