Preimmunization correlates of protection shared across malaria vaccine trials in adults

Identifying preimmunization biological characteristics that promote an effective vaccine response offers opportunities for illuminating the critical immunological mechanisms that confer vaccine-induced protection, for developing adjuvant strategies, and for tailoring vaccination regimens to individuals or groups. In the context of malaria vaccine research, studying preimmunization correlates of protection can help address the need for a widely effective malaria vaccine, which remains elusive. In this study, common preimmunization correlates of protection were identified using transcriptomic data from four independent, heterogeneous malaria vaccine trials in adults. Systems-based analyses showed that a moderately elevated inflammatory state prior to immunization was associated with protection against malaria challenge. Functional profiling of protection-associated genes revealed the importance of several inflammatory pathways, including TLR signaling. These findings, which echo previous studies that associated enhanced preimmunization inflammation with protection, illuminate common baseline characteristics that set the stage for an effective vaccine response across diverse malaria vaccine strategies in adults.

COVID-19 Vaccine Perceptions in the Initial Phases of US Vaccine Roll-out: An Observational Study on Reddit

Background: Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions early in the vaccine timeline. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements, in the initial phases of the vaccine timeline. Methods: We collected all posts on Reddit from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits. Results: There was an association between a Pfizer press release reporting 90\% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, NoNewNormal). Conclusions: Our findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions, early in the vaccine timeline. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines, especially in the early phases of vaccine roll-out. Further research is needed to understand how social media can contribute to COVID-19 vaccination services.

COVID-19 vaccine trials with children: ethics pointers

As healthcare authorities around the world strive to get as many citizens as possible vaccinated against the SAR-CoV-2 virus, many countries have begun including children in the population groups to be vaccinated. Properly designed clinical trials involving children are important to ensure safety, efficacy, and dosage of therapies in (developing) children. Within the complex health, social, and political scenario of the ongoing pandemic, ethics committees and policy makers in low-income and middle-income settings need to consider additional ethical questions when called on to review phase III COVID-19 vaccine trials involving in children. We set out some of the ethical questions to keep in mind before, during, and after the implementation of phase III COVID-19 vaccine trials in limited resource settings. Specifically, we discuss and offer succinct answers to the following questions: How relevant will the trial vaccine be for the population participating in the trial? Should vaccines that have not been approved for use among adults be approved for use in trials with children? Which children should be involved in COVID-19 vaccine trials? What criteria of informed consent are to be adopted with minors? Placebo versus an existing already approved vaccine? What specific duties of ancillary care should be taken into consideration for COVID-19 vaccines especially in low-income and middle-income countries? The answers we offer are considerations that can serve as ‘things to think about’ when reviewing or implementing COVID-19 trials involving children in low-income settings.

COVID-19 Vaccination Compliance and Associated Factors among Medical Students during an Early Phase of Vaccination Rollout—A Survey from Israel

COVID-19 is “a once-in-a-century” pandemic, bringing with it unparalleled health, social, and economic ramifications. As part of the world’s efforts to restrain the pandemic, vaccine development has been expedited. This population-representative survey in Israel aimed to investigate whether the knowledge, attitudes, and vaccination status of medical students affect their intention to recommend COVID-19 vaccination (as well as reasons for refusal and acceptance of the vaccine). The questionnaire was anonymous, via Google Forms app in December 2021. One-hundred and four medical students completed the survey. Overwhelmingly, (91.3%) COVID-19 vaccination status and intention to receive the vaccine were positively associated with intention to recommend. Twenty-five percent of the students replied that they lacked knowledge regarding the vaccine. A statistically significant association was found between experiencing quarantine and the intention to be vaccinated (p = 0.034). There was a significant positive relationship between the number of symptoms from previous vaccines and the fear of COVID-19 (rs = 0.272, p < 0.01). Prior vaccination did not have an effect on COVID-19 vaccine hesitancy. This first study evaluating COVID-19 vaccine hesitancy among Israeli medical students highlighted the need for medical programs to emphasize the benefits of COVID-19 vaccination in the protection of healthcare workers and patient safety. Education, awareness campaigns, and regulation of vaccine trials could further decrease COVID-19 vaccine hesitancy and increase vaccine rates among medical students.

The O-Ag Antibody Response to Francisella Is Distinct in Rodents and Higher Animals and Can Serve as a Correlate of Protection

Identifying correlates of protection (COPs) for vaccines against lethal human (Hu) pathogens, such as Francisella tularensis (Ft), is problematic, as clinical trials are currently untenable and the relevance of various animal models can be controversial. Previously, Hu trials with the live vaccine strain (LVS) demonstrated ~80% vaccine efficacy against low dose (~50 CFU) challenge; however, protection deteriorated with higher challenge doses (~2000 CFU of SchuS4) and no COPs were established. Here, we describe our efforts to develop clinically relevant, humoral COPs applicable to high-dose, aerosol challenge with S4. First, our serosurvey of LVS-vaccinated Hu and animals revealed that rabbits (Rbs), but not rodents, recapitulate the Hu O-Ag dependent Ab response to Ft. Next, we assayed Rbs immunized with distinct S4-based vaccine candidates (S4ΔclpB, S4ΔguaBA, and S4ΔaroD) and found that, across multiple vaccines, the %O-Ag dep Ab trended with vaccine efficacy. Among S4ΔguaBA-vaccinated Rbs, the %O-Ag dep Ab in pre-challenge plasma was significantly higher in survivors than in non-survivors; a cut-off of >70% O-Ag dep Ab predicted survival with high sensitivity and specificity. Finally, we found this COP in 80% of LVS-vaccinated Hu plasma samples as expected for a vaccine with 80% Hu efficacy. Collectively, the %O-Ag dep Ab response is a bona fide COP for S4ΔguaBA-vaccinated Rb and holds significant promise for guiding vaccine trials with higher animals.

Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1–28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.

COVID-19 vaccine and immune response

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; βCoV), the causative agent of coronavirus disease 2019 (COVID-19), causes severe lower respiratory tract infections and acute respiratory failure syndrome (ARDS). Deaths due to the ongoing COVID-19 pandemic for more than a year are still seen worldwide. Therefore, vaccine trials have gained importance. The discovery of the genome and protein structure of SARS-CoV-2 in a short time allowed the development of nucleic acid-based vaccines (mRNA and DNA vaccines), vector vaccines, inactivated virus vaccines, protein-based vaccines, virus-like particle vaccines, and live attenuated virus vaccines. Many companies, universities, and institutes around the world continue to develop effective vaccines against SARS-CoV-2. In this review, the structural features, classification, genome, and intracellular entry of SARS-CoV-2 coronaviruses, stimulation of the immune system and immunity, COVID-19 vaccine types, and the latest status of clinical trials of these vaccines have been reviewed.

Equity in Vaccine Trials for Higher Weight People? A Rapid Review of Weight-Related Inclusion and Exclusion Criteria for COVID-19 Clinical Trials

Higher weight status, defined as body mass index (BMI) ≥ 30 kg/m2, is frequently described as a risk factor for severity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (known as COVID-19). Therefore, study groups in COVID-19 vaccine trials should be representative of the weight spectrum across the global population. Appropriate subgroup analysis should be conducted to ensure equitable vaccine outcomes for higher weight people. In this study, inclusion and exclusion criteria of registered clinical trial protocols were reviewed to determine the proportion of trials including higher weight people, and the proportion of trials conducting subgroup analyses of efficacy by BMI. Eligibility criteria of 249 trial protocols (phase I, II, III and IV) were analysed; 51 protocols (20.5%) specified inclusion of BMI > 30, 73 (29.3%) specified exclusion of BMI > 30, and 125 (50.2%) did not specify whether BMI was an inclusion or exclusion criterion, or if BMI was included in any ‘health’ screenings or physical examinations during recruitment. Of the 58 protocols for trials in phase III and IV, only 2 (3.4%) indicated an intention to report subgroup analysis of vaccine efficacy by weight status. Higher weight people appear to be significantly under-represented in the majority of vaccine trials. This may result in reduced efficacy and acceptance of COVID-19 vaccines for higher weight people and exacerbation of health inequities within this population group. Explicit inclusion of higher weight people in COVID-19 vaccine trials is required to reduce health inequities.