Vaccine Safety Research Articles

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR−/− mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 ​μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.

Enhancing protective immunity against bacterial infection via coating nano-Rehmannia glutinosa polysaccharide with outer membrane vesicles.

With the coming of the post-antibiotic era, there is an increasingly urgent need for safe and efficient antibacterial vaccines. Bacterial outer membrane vesicles (OMVs) have received increased attention recently as a potential subunit vaccine. OMVs are non-replicative and contain the principle immunogenic bacterial antigen, which circumvents the safety concerns of live-attenuated vaccines. Here, we developed a novel nano-vaccine by coating OMVs onto PEGylated nano-Rehmannia glutinosa polysaccharide (pRL) in a structure consisting of concentric circles, resulting in a more stable vaccine with improved immunogenicity. The immunological function of the pRL-OMV formulation was evaluated in vivo and in vitro, and the underlying mechanism was studied though transcriptomic analysis. The pRL-OMV formulation significantly increased dendritic cell (DC) proliferation and cytokine secretion. Efficient phagocytosis of the formulation by DCs was accompanied by DC maturation. Further, the formulation demonstrated superior lymph node targeting, contributing to a potent mixed cellular response and bacterial-specific antibody response against Bordetella bronchiseptica infection. Specifically, transcriptomic analysis revealed that the immune protection function correlated with T-cell receptor signalling and Th1/Th2/Th17 differentiation, among other markers of enhanced immunological activity. These findings have implications for the future application of OMV-coated nano-carriers in antimicrobial immunotherapy.

Medical occurrence and safety of SARS-CoV-2 vaccination outside of the hospital setting.

During COVID-19 pandemic, vaccination has been strongly recommended and advocated to prevent COVID-19 infection and adverse outcomes, particularly among at-risk populations. The vaccination against SARS-CoV-2 (COVAC) occurred at off-site locations capable of accommodating large crowds, distinct from the hospital setting, where a team of intensivists, emergency physicians, and nurses, ensuring prompt medical attention (medical occurrences, MO) in cases of adverse event following immunization. Our aims were to estimate the incidence of MO, and to assess its association with demographics, and vaccine characteristics. Our retrospective cohort study included all subject aged 12years and older who received vaccinations at two large out-of-hospital vaccination hubs (Fiera Milano City, Palazzo delle Scintille), between April 12th and August 31st, 2021. Nine hundred and ninety-five thousand and twenty-eight vaccinations were administrated. MOs incidence rate was 278/100,000 doses (95% confidence interval (CI) 268-289). Most MOs were mild (86.27%) and mainly observed in subjects who received the Comirnaty vaccine; 92 MOs (3.32%) were severe and mostly occurred in recipients of the Vaxzeria vaccine. The incidence rate for hospital transfers following vaccination was 4.7/100,000 doses (95% CI 3.5-6.2) and any level of anaphylaxis occurred in 0.4 cases per 100,000 administrated doses (95% CI 0.3.-0.7). Sex, age, type of vaccine and first dose were associated with incidence of MO. Our results showed a low incidence rate in MOs after COVAC, mainly mild and support the feasibility, effectiveness and safety of vaccinations administered in hubs with a dedicated SEU located outside of the hospital setting.

Improving Beef Cattle Production: Safety and Effectiveness of New Immunocastration Vaccine.

Reproductive control in mammals, particularly in beef production systems, is crucial for managing behaviors driven by sex steroids, which can cause biosecurity issues, reduced weight gain, and decreased meat quality. Additionally, controlling sexual activity in females prevents unwanted pregnancies when both sexes are housed together for fattening. Surgical castration in cattle, commonly performed under field conditions, is associated with significant welfare concerns due to pain and infection risks. Furthermore, castrating female cattle in the field is often impractically expensive. Hence, new reproductive control methods that prioritize animal welfare and are suitable for both sexes are essential. Immunocastration (IC), which involves vaccination against the GnRH-I hormone, has emerged as a promising alternative, demonstrating efficacy and safety in various species. Immunocastration has proven to be an effective alternative to surgical castration in controlling reproduction and promoting animal welfare in several species. This study aims to evaluate the safety, immunogenicity, immunocastration effect, and productive impact of a novel IC vaccine developed in Chile for female cattle. Two consecutive trials were conducted, the first under controlled conditions and the second under field conditions. The results demonstrated that the new vaccine is safe and effective for use in beef cattle, inducing specific immunity against GnRH-I, reducing gonadal functionality, and improving productive parameters. These findings suggest that this new IC vaccine can significantly benefit the beef cattle industry by providing a welfare-friendly and efficient method of reproductive control.

Indonesian Mothers' Experience of Their Daughter's HPV Vaccination, and Factors Associated with Their Willingness to Recommend HPV Vaccination for Girls.

In Indonesia, knowledge of parents' experiences of their daughters' HPV vaccination in school settings is limited. As Indonesia seeks to scale up its HPV vaccination program nationwide, parents' perspectives hold important insights into how elements of the vaccination model can be sustained and improved. This study explored mothers' experiences of their daughters' HPV vaccination experiences, their knowledge of HPV risks and prevention, and factors associated with willingness to recommend HPV vaccination for girls. A cross-sectional online survey was conducted with 143 mothers of schoolgirls who had received HPV vaccination at schools in Yogyakarta and Jakarta. Multivariate logistic regression was used to assess factors associated with willingness to recommend HPV vaccination. Chi-square and independent t-tests were performed to assess relationships between variables. One-way ANOVA was used to test mean differences in knowledge scores among mothers with different education levels. Many respondents (62.4%) received key health information before their daughters' HPV vaccination. Mothers' average knowledge score was 6.07/10 (SD 2.35). Receiving satisfactory information was significantly associated with willingness to recommend HPV vaccination for girls to others. A significant association was found between mothers' willingness to recommend HPV vaccination and having ever participated in cervical cancer screening themselves. Providing consistent health information that addresses the knowledge gaps and affirms the benefits and safety of HPV vaccines can improve the likelihood of mothers recommending HPV vaccination to others. The benefit of a synchronized approach to promoting primary and secondary prevention was supported by the findings.

Efficacy and safety of therapeutic vaccines for the treatment of chronic hepatitis B: A systematic review and meta-analysis of randomized controlled trials update.

Most people diagnosed with chronic hepatitis B (CHB) need treatment to help reduce the risk of liver disease and limit disease transmission. Therapeutic vaccine (TV) candidates have been under study for their clinical effects on inducing HBV-specific host immune responses. This review aimed to systematically synthesize updated evidence on the efficacy and safety of TVs in patients with CHB. This systematic review was performed by searching different databases from January to February 2021. Completed randomized controlled trials that reported TVs' efficacy and/or safety for treating CHB compared with the standard of care (SOC) or placebo were included. Efficacy and safety estimates were reported as the logarithm of the odds ratio and risk differences, respectively. I2 > 50% was considered significant heterogeneity. Significant publication bias was considered when Egger's test P value < .10. The risk of bias was assessed using the Cochrane Risk of Bias tool. The GRADE methodology was used to assess the certainty of the evidence for each outcome. Twenty-four articles with 2889 pooled samples were included. TVs made a significant difference in hepatitis B envelope antigen (HBeAg) SC (log OR = 0.76, P = .01) and (log OR = 0.40, P = .03) compared to placebo and combination therapy, respectively. HBeAg SC was significantly affected by TVs at the end of follow up (log OR = 0.49, P = .01), with significant HBsAg mean difference (MD = -0.62, P = .00). At the end of treatment, the TVs had no significant effect on HBV DNA negativity over the SOC (log OR = 0.62, P = .09) or placebo (log OR = -0.07, P = .91). TVs do not significantly affect the risk of serious adverse events (RD 0.02, 95% CI 0.00-0.04). In patients with CHB, TVs had significant effects on HBeAg SC compared to the SOC or placebo. There was no significant difference between serious adverse events. TVs are promising treatment strategy to overcome CHB.

Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 − 25.8] vs 46.4 [40.6 − 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% − 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.

The Role of Risk Perception and Big Five Personality Traits in COVID-19 Vaccine Hesitancy in Indonesia

Even when the COVID-19 global health emergency is declared over, vaccine hesitancy is a relevant topic that needs to be studied to ensure effective intervention when such cases arise again in the future. Vaccine hesitancy is a phenomenon of public doubt about whether to accept or reject vaccination. This study aims to determine the characteristics of vaccine hesitancy in Indonesian society and its relationship with the risk perception of COVID-19 and the Big Five personality traits. We also discuss how the present findings can inform future decision making on pandemic interventions. This multimethod cross-sectional study incorporated both quantitative and qualitative analyses through self-report measures and an open question. We distributed the questionnaire online through convenience sampling technique and involved 390 Indonesian citizens aged 18-62 years (Mage = 30.68, SD = +13.17). Through regression analyses, we found that risk perception of COVID-19, Extraversion, Conscientiousness, and Intellect were significant predictors of vaccine hesitancy. Thematic analysis showed that themes of lack of confidence, convenience, and complacency were present in participants’ attitudes toward COVID-19 vaccines. Demographic analysis also showed a correlation between vaccine hesitancy and economic status. Vaccination campaigns should focus on extensive education on vaccine safety that is backed by factual data, education on the risk of preventable diseases with vaccination, and increasing public confidence in government and health authorities.

Ad26.M.Env ZIKV vaccine protects pregnant rhesus macaques and fetuses against Zika virus infection

At the start of the Zika virus (ZIKV) epidemic in 2015, ZIKV spread across South and Central America, and reached parts of the southern United States placing pregnant women at risk for fetal microcephaly, fetal loss, and other adverse pregnancy outcomes associated with congenital ZIKA syndrome (CZS). For this reason, testing of a safe and efficacious ZIKV vaccine remains a global health priority. Here we report that a single immunization with Ad26.M.Env ZIKV vaccine, when administered prior to conception, fully protects pregnant rhesus macaques from ZIKV viral RNA in blood and tissues with no adverse effects in dams and fetuses. Furthermore, vaccination prevents ZIKV distribution to fetal tissues including the brain. ZIKV associated neuropathology was absent in offspring of Ad26.M.Env vaccinated dams, although pathology was limited in fetuses from non-immunized, challenged dams. Vaccine efficacy is associated with induction of ZIKV neutralizing antibodies in pregnant rhesus macaques. These data suggest the feasibility of vaccine prevention of CZS in humans.

COVID-19 vaccine hesitancy: Meaning relations between responses in an epidemiological study and twitter messages

BackgroundVaccine hesitancy is a concerning public health issue, further amplified during the COVID-19 pandemic. Social media is an important player in this context, promoting the dissemination of both information and misinformation. Qualitative studies analyzing the meaning of social media contents in correlation with epidemiological data are scarce, and could aid our understanding of social media's impact on vaccine hesitancy. MethodsIn this study, we identified open-ended responses on reasons to refuse the COVID-19 vaccine collected in an epidemiologic study, and analyzed meaning relations with Twitter posts according to theme categories using a qualitative approach. ResultsAmong responses to open-ended questions on motivations for refusing the COVID-19 vaccine, we identified and analyzed five theme categories: 1. individuality; 2. fear of adverse events/distrust in vaccine safety; 3. political ideologies/aversion to recommendations issued by the State; 4. skepticism about vaccine efficacy; and 5. refusal of non-natural products or interventions. We observed a close correspondence between open-ended responses in the epidemiological study and Twitter posts in all 5 theme categories. The highest outreach of Twitter posts was observed for those in the “individuality” and “fear of adverse the events/distrust in vaccine safety” theme categories. ConclusionsOur study suggests that social media interactions can perpetuate misinformation and hesitant attitudes about vaccines. Social media algorithms can intensify ideologic isolation, and strategies to promote the dissemination of tailored health information among social media users should be implemented to promote an overall understanding of health, particularly those concerning the collective wellbeing.

Immunogenicity and Safety of Chikungunya Vaccines: A Systematic Review and Meta-Analysis.

Several vaccines against chikungunya fever have been developed and tested, and one has been recently licensed. We performed a meta-analysis to estimate the immunogenicity and safety of all chikungunya vaccines that have been progressed to clinical trial evaluation (VLA1553; mRNA-1388/VAL-181388; PXVX0317/VRC-CHKVLP059-00-VP; ChAdOx1 Chik; MV-CHIK). We included trials retrieved from MedLine, Scopus, and ClinicalTrials.gov. The outcomes were the rates of seroconversion/seroresponse and serious adverse events (SAEs) after the primary immunization course. We retrieved a total of 14 datasets, including >4000 participants. All candidate chikungunya vaccines were able to elicit an immunogenic response in ≥96% of vaccinated subjects, regardless of the vaccination schedule and platform used, and the seroconversion/seroresponse rates remained high 6 to 12 months after vaccination for most vaccines. Four of the five candidate vaccines showed a good overall safety profile (no data were available for ChAdOx1 Chik), with no significant increase in the risk of SAEs among the vaccinated, and a low absolute risk of product-related SAEs. Overall, the present findings support the potential use of the candidate vaccines for the prevention of chikungunya and the current indication for use in adult travelers to endemic regions of the licensed VLA 1553 vaccine. In order to extend chikungunya vaccination to a wider audience, further studies are needed on individuals from endemic countries and frail populations.

A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4–5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.

Short-Term Active Safety Surveillance of the Spikevax and Nuvaxovid Priming Doses in Australia.

Australia commenced administration of the Spikevax (Moderna mRNA-1273) COVID-19 vaccine in August 2021 and Nuvaxovid (Novavax NVX-CoV2373) in January 2022. This study describes the short-term safety profile of priming doses of the Spikevax and Nuvaxovid vaccines given between September 2021 and September 2023. Online surveys were sent via AusVaxSafety, Australia's active vaccine safety surveillance system, three and eight days after vaccination. A total of 131,775 day 3 surveys were sent, with a response rate of 38.5% (N = 50,721). A total of 43,875 day 8 surveys matched with day 3 survey responses were sent, with a response rate of 71.5% (N = 31,355). Half (50.7%) of respondents reported any adverse event following immunisation (AEFI) in the 0-3 days after vaccination and 24.6% reported any AEFI 4-7 days after vaccination. Fatigue, local pain, headache, and myalgia were the most frequently reported symptoms for both vaccines in both periods. After adjusting for respondent characteristics, vaccination clinic type, jurisdiction, and medical conditions, the odds for reporting AEFI increased with age from 16-19 years to highest odds at 30-39 years, after which it declined. Females had greater odd of reporting AEFI than males across most age groups, vaccine types, and doses. Respondents with a history of anaphylaxis had greater odds of reporting any AEFI (adjusted OR range: 1.50-2.86). A total of 3.1% of respondents reported seeking medical review 0-3 days after vaccination. This study affirms the short-term safety of Spikevax and Nuvaxovid COVID-19 vaccine priming doses in a large sample in Australia.

Endurance Exercise Does Not Exacerbate Cardiac Inflammation in BALB/c Mice Following mRNA COVID-19 Vaccination.

The mechanism underlying myopericarditis associated with mRNA COVID-19 vaccination, including increased susceptibility in young males, remains poorly understood. This study aims to explore the hypothesis that engaging in physical exercise at the time of mRNA COVID-19 vaccination may promote a cardiac inflammatory response, leading to the development of myopericarditis. Male BALB/c mice underwent treadmill running or remained sedentary for five weeks. Subsequently, two doses of the Pfizer/BioNTech vaccine or vehicle were administered with a 14-day interval, while the exercise regimen continued. The animals were euthanized days after the second vaccination. Vaccination was followed by body weight loss, increased hepatic inflammation, and an antigen-specific T cell response. Small foci of fibrovascular inflammation and focal cell loss were observed in the right ventricle, irrespective of vaccination and/or exercise. Vaccination did not elevate cardiac troponin levels. Cardiac tissue from the vaccinated mice showed upregulated mRNA expression of the genes IFNγ and IL-1β, but not IL-6 or TNFα. This pro-inflammatory signature in the heart was not exacerbated by endurance exercise. Ex vivo vascular reactivity remained unaffected by vaccination. Our data provide evidence for the cardiac safety of mRNA COVID-19 vaccination. The role of exercise in the development of pro-inflammatory cardiac changes post mRNA vaccination could not be established.

Challenges in the Application of African Swine Fever Vaccines in Asia.

This paper explores the significance of quality vaccines in managing ASF in Asia, where it poses a substantial threat to the pork industry. It emphasizes the risks associated with substandard vaccines, including the emergence of new virus strains that complicate disease control. Highlighting recent advancements in vaccine deployment in Vietnam, the paper calls for rigorous testing and regulations to guarantee vaccine effectiveness and safety. The authors advocate for the implementation of vaccines with the inclusion of differentiating infected from vaccinated animals (DIVA), which enhances disease management strategies in both endemic and non-endemic regions. The conclusion underscores the necessity of stringent standards in vaccine development and strict adherence to regulatory guidelines to ensure successful ASF management and maintain public trust in the vaccines.

Towards Safe African Swine Fever Vaccines: The A137R Gene as a Tool to Reduce Virulence and a Promising Serological DIVA Marker Candidate.

African swine fever (ASF) is an emerging disease caused by the African swine fever virus (ASFV), which is a great threat to the swine industry worldwide. Currently registered vaccines that have demonstrated protection against the homologous ASFV strains are live attenuated vaccines based on recombinant ASFV strains with the deletions of virulence-associated genes. In this study, we evaluated the deletion of the A137R gene in the ASFV virulent Stavropol_01/08 strain isolated in Russia in 2008. Our animal experiment results demonstrated that the deletion of the A137R gene did not lead to the full attenuation of this strain, and increasing the dose of the A137R-deletion mutant during infection led to the death of 87.5% of the infected animals. In this report, we also demonstrated that immunofluorescence (IFA) and Western blotting assays based on the recombinant p11.5 protein can be used to detect antibodies in animals infected with the attenuated ASFV variants of several genotypes/serotypes. Both assays were specific to ASFV p11.5 protein and showed negative results when examining the sera of the non-infected animals or those infected with the A137R-deletion mutant. Therefore, we propose to use the p11.5 protein along with other previously proposed ASFV proteins, such as CD2v, as negative antigenic DIVA markers for an attenuated ASF vaccine.

A Survey on Population Perceived Factors Influencing COVID-19 Vaccination in South Indian Districts.

The COVID-19 pandemic has posed unprecedented challenges to global public health, necessitating the rapid development and distribution of vaccines. Despite the availability of effective vaccines, vaccination uptake remains varied across different regions and populations. This study aims to investigate the factors influencing COVID-19 vaccination uptake in South Indian districts, with a focus on understanding public perceptions. Utilizing a cross-sectional survey methodology, data were collected from a representative sample of residents in selected South Indian districts. The survey explored a range of variables including demographic characteristics, knowledge and awareness about COVID-19 vaccines, perceived risks and benefits, trust in healthcare systems, and sources of vaccine-related information. The preliminary analysis indicates that vaccine uptake is significantly influenced by factors such as age, educational level, and socioeconomic status. High levels of vaccine hesitancy were associated with misinformation, concerns about vaccine safety and efficacy, and distrust in government and healthcare authorities. Conversely, individuals with higher education levels and those who received accurate information from trusted sources showed a greater willingness to get vaccinated. Social and cultural beliefs also played a crucial role in influencing vaccination attitudes, stressing the need for the importance of culturally sensitive health communication strategies.The study investigates a range of factors, including demographic characteristics such as age, gender, education level, and socio-economic status, as well as psychological and social determinants like the perceived risk of COVID-19, trust in vaccines, and the influence of misinformation. This study underscores the need for targeted public health interventions to address vaccine hesitancy and improve vaccination rates in South India. By identifying the key factors influencing vaccination decisions, policymakers and healthcare providers can develop more effective communication and outreach programs tailored to the unique needs and concerns of the population. Enhanced efforts in education, transparency, and community engagement are essential to fostering greater public trust and achieving higher vaccination coverage.

Discovering vaccines: the trial tale.

This paper reviews the importance of vaccine trials to public health. Vaccines are developed to build immunity to disease, which have helped to completely eliminate smallpox, and reduced incidence of polio and measles. A variety of breakthroughs made many years ago, such as the smallpox vaccine by Edward Jenner and the discoveries by Louis Pasteur, also set the stage for modern international immunization programs. A few events, such as the licensing of the polio vaccine and the passage of the Vaccination Assistance Act helped to improve the study of vaccines. In particular, vaccine trials may be RCTs, cluster trials, or cohort studies. The sample sizes will depend on the objectives, which would include the primary and secondary endpoints. The population under study and the geographical location also affect the trial design. Preclinical evaluation is usually the starting point of vaccine trials, where the safety and efficacy are researched on animal models or cell cultures. Animal models are selected based on their similarity to the target disease. Safety is checked in Phase I, efficacy in Phase II, and both in Phase III. Phase IV is a post-marketing surveillance of the vaccine's safety in real life. Regulatory bodies play a very vital role in ensuring that vaccines adhere to a very high standard of safety and efficacy, such as the FDA, as required. Ethical considerations, such as informed consent and the rights of participants, are innate and are implemented and enforced through laws, regulations, and ethical committees. Vaccine studies vary from the drug studies as it is focused on preventing illness in healthy patients as opposed to cure of diseases in drug trials. The dramatic development in vaccine research was driven by recent pandemics, with parallel processing and data collection in real time. Clinical trials of the vaccine are a foundation stone of public health in the reduction of sickness, offering immunity to diseases, and continuing the fight against infectious diseases. The present review is aimed at describing vaccine trials and their important aspects.

Safety and Immunogenicity of Trivalent Oral Polio Vaccine in Vaccinated Children and Vaccine-Naïve Infants: A Phase 4 Study.

In the context of polio eradication, novel oral polio vaccines for type 2 (nOPV2) were developed, and types 1 and 3 polioviruses are being developed. We aimed to generate trivalent oral poliovirus vaccine (tOPV) safety and immunogenicity data as a reference for comparing with novel OPV formulations. This was a single-center, open-label, phase 4 study in March 2016 in the Dominican Republic with healthy children previously vaccinated with ≥3 doses of tOPV receiving one dose of tOPV and vaccine-naïve infants receiving 3 doses of tOPV. Safety and immunogenicity were assessed. No serious adverse reactions or important medical reactions were reported. Seroconversion (SC) rates at Day 28 in children were 32.7%, 36.7%, and 46.9% for types 1, 2, and 3, respectively, and seroprotection (SP) rates 28 days after one dose increased from 89.8% at baseline to 93.9%, 98.0% to 100%, and 83.7% to 98.0% for types 1, 2, and 3, respectively. In infants, SC rates were 88.5%, 98.1%, and 96.2% for types 1, 2, and 3, respectively. SP rates at Day 84 were 93.3%, 100%, and 96.2% for types 1, 2, and 3, respectively. This information can be used as a reference to compare with novel monovalent or trivalent OPVs under development.

Antibody response of endangered riparian brush rabbits to vaccination against rabbit hemorrhagic disease virus 2.

Rabbit hemorrhagic disease virus 2 (RHDV2; Caliciviridae, Lagovirus europaeus), the cause of a highly transmissible and fatal lagomorph disease, has spread rapidly through the western United States and Mexico, resulting in substantial mortality in domestic and wild rabbits. The disease was first detected in California in May 2020, prompting an interagency/zoo/academia/nonprofit team to implement emergency conservation actions to protect endangered riparian brush rabbits (Sylvilagus bachmani riparius) from RHDV2. Prior to vaccinating wild rabbits, we conducted a vaccine safety trial by giving a single SC dose of Filavac VHD K C+V (Filavie) vaccine to 19 adult wild riparian brush rabbits captured and temporarily held in captivity. Rabbits were monitored for adverse effects, and serum was collected before vaccination, and at 7-10, 14-20, and 60 d post-vaccination. Sera were tested using an ELISA to determine antibody response and timing of seroconversion. Reverse-transcription quantitative real-time PCR (RT-qPCR) was performed on rectal swabs to evaluate infection status. No adverse effects from the vaccine were observed. Before vaccination, 18 of 19 rabbits were seronegative, and RHDV2 was not detected by RT-qPCR on any rectal swabs. After vaccination, all rabbits developed an antibody response, with titers of 1:10-1:160. Seroconversion generally occurred at 7-10 d. The duration of antibody response was ≥60 d in 12 of 13 rabbits. Sixteen animals were released and 4 were recaptured several months later, offering a glimpse into longer duration immune response. Our study has informed vaccination strategies for this species and serves as a model for protecting other vulnerable lagomorphs against RHDV2.