Vaccine Safety Research Articles

An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 μg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 μg and 20 μg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

Knowledge, Attitude, and Perception Regarding the Human Papillomavirus (HPV) Vaccine Among Parents at Al-Madinah Al-Munawwar: A Cross-Sectional Study.

Human papillomavirus (HPV)is the leading cause of cervical cancer in reproductive-age Saudi women. Parents' understanding and attitude regarding HPV vaccination in young girls are vital to preventing cervical cancer. This study aims to assess the knowledge, attitudes, and perceptions of parents in Al-Madinah Al-Munawwara towards the HPV vaccine and identify factors influencing their decision to vaccinate their children. A cross-sectional survey was conducted among 500 parents in Al-Madinah Al-Munawwara. A structured questionnaire was used to collect data on demographics, knowledge about HPV and the HPV vaccine, attitudes towards vaccination, and perceptions of vaccine safety and efficacy. Data were analyzed using Statistical Product and Service Solutions (SPSS, version 21; IBM SPSS Statistics for Windows, Armonk, NY). Parents have 57.6% knowledge about HPV, 69.2% perceive it as dangerous, and 29.8% know its link to cervical cancer. Physicians are the primary source, and 81.2% believe the vaccine protects HPV. Key predictors of vaccine acceptance included higher educational levels, awareness of HPV-related health risks, and recommendations from healthcare professionals. The study reveals a lack of knowledge about HPV infection and vaccines among Saudi Arabian parents, with only 7.2% having vaccinated their children, emphasizing the need for education and screening programs.

Tinnitus after COVID-19 vaccination: Findings from the vaccine adverse event reporting system and the vaccine safety datalink

PurposeTo assess the occurrence of tinnitus following COVID-19 vaccination using data mining and descriptive analyses in two U.S. vaccine safety surveillance systems. MethodsReports of tinnitus after COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS) from 2020 through 2024 were examined using empirical Bayesian data mining and by calculating reporting rates. In the Vaccine Safety Datalink (VSD) population, ICD-10 coded post-vaccination medical visits were examined using tree-based data mining, and tinnitus visit incidence rates during post-vaccination days 1–140 were calculated by age group for COVID-19 vaccines and for comparison, influenza vaccine. ResultsVAERS data mining did not find disproportionate reporting of tinnitus for any COVID-19 vaccine. VAERS received up to 84.82 tinnitus reports per million COVID-19 vaccine doses administered. VSD tree-based data mining found no signals for tinnitus. VSD tinnitus visit incidence rates after COVID-19 vaccines were similar to those after influenza vaccine except for the group aged ≥65 years (Moderna COVID-19 vaccine, 165 per 10,000 person-years; Pfizer-BioNTech COVID-19 vaccine, 154; influenza vaccine, 135). ConclusionsOverall, these findings do not support an increased risk of tinnitus following COVID-19 vaccination but cannot definitively exclude the possibility. Descriptive comparisons between COVID-19 and influenza vaccines were limited by lack of adjustment for potential confounding factors.

Cardiac rehabilitation patient perspectives during COVID-19 pandemic: quantitative and qualitative study.

This study aimed to quantitatively assess stress, anxiety and obsessive thinking related to coronavirus disease-19 (COVID-19) and qualitatively appraise perceptions in patients after acute myocardial infarction (AMI) undergoing cardiac rehabilitation (CR) during the COVID-19 pandemic. We used mixed-methods design in patients referred for CR in 2 centres which delivered uninterrupted service during COVID-19 pandemic. Coronavirus Anxiety Scale (CAS), Obsession with COVID-19 Scale (OCS), COVID-19 Stress Scale (CSS), Hospital Anxiety and Depression Scale (HADS), and in-person interviews (combination of a priori questions and probing) were used to evaluate patient experience and perceptions with COVID-19 and the healthcare services during pandemic. In total, 109 patients (mean age 59 ± 10, 20% women) were included in quantitative part and in 30 of them we conducted the in-person interviews. About a quarter of patients met HADS threshold for anxiety and depression while CAS and OCS results demonstrated extremely low possibility of coronavirus related dysfunctional thinking (3%) and anxiety (2%). The CSS indicated the most prevalent concerns were related to COVID-19 vaccines safety (60%) and fear of getting infected (60%). During interviews, patients perceived the CR as well as health care providers as safe, trustworthy and with enough support to avoid or manage COVID-19 related health risks. Overall, patients reported AMI affected their lives more than the COVID-19 pandemic. The COVID-19 related stress and anxiety were relatively low and mostly related to general views of infectious disease. CR was perceived safe and trustworthy in terms of primary disease and COVID-19. This mixed-method study included 109 patients with acute myocardial infarction who underwent cardiac rehabilitation during the COVID-19 and focused on their experience and perceptions with COVID-19 and the healthcare services during pandemic.-Patients reported acute myocardial infarction affected their lives more than the COVID-19 pandemic.-The COVID-19 related concerns were mostly related to general views of infectious disease (vaccine safety, fear of getting infected) whilst cardiac rehabilitation was perceived safe and trustworthy environment during COVID-19.

COVID-19 and influenza vaccine-hesitancy subgroups.

Health communicators are faced with the challenge that people can hesitate vaccines for different reasons. Our aim was to identify and describe the qualities of distinct COVID-19 and influenza vaccine-hesitancy subgroups to facilitate the development of tailored vaccine-hesitancy communication. In two studies, we used agglomerative hierarchical cluster analysis to identify COVID-19 (N = 554) and influenza (N = 539) vaccine-hesitancy subgroups in the general population based on nine vaccine hesitancy-related variables (intent to get vaccinated, perceived vaccine safety, perceived vaccine efficacy, perceived disease threat, perceived vaccination responsibility, perceived vaccination convenience, distrust in authorities, conspiracy mentality, and reliance on anecdotal testimonies). We identified and described six distinct COVID-19 vaccine-hesitancy subgroups (the Vaccination Positive, the Ambivalent, the Fearing Skeptic, the Unconvinced, the Constrained Skeptic, and the Vaccination Opponent), and three influenza vaccine-hesitancy subgroups (the Vaccination Positive, the Complacent, and the Vaccination Opponent), with different levels of hesitancy. We discuss the implications of the results for health communicators. Our results shed light on the (dis)similarities between people who hesitate COVID-19 and influenza vaccines and suggest that there is greater variety in hesitancy concerning COVID-19 vaccinations than influenza vaccinations. These findings can be used to design and test tailored vaccination messages.

Preferences for COVID-19 Vaccines: Systematic Literature Review of Discrete Choice Experiments.

Vaccination can be viewed as comprising the most important defensive barriers to protect susceptible groups from infection. However, vaccine hesitancy for COVID-19 is widespread worldwide. We aimed to systematically review studies eliciting the COVID-19 vaccine preference using discrete choice experiments. A literature search was conducted in PubMed, Embase, Web of Science, Scopus, and CINAHL Plus platforms in April 2023. Search terms included discrete choice experiments, COVID-19, and vaccines and related synonyms. Descriptive statistics were used to summarize the study characteristics. Subgroup analyses were performed by factors such as high-income countries and low- and middle-income countries and study period (before, during, and after the pandemic wave). Quality appraisal was performed using the 5-item Purpose, Respondents, Explanation, Findings, and Significance checklist. The search yield a total of 623 records, and 47 studies with 53 data points were finally included. Attributes were grouped into 4 categories: outcome, process, cost, and others. The vaccine effectiveness (21/53, 40%) and safety (7/53, 13%) were the most frequently reported and important attributes. Subgroup analyses showed that vaccine effectiveness was the most important attribute, although the preference varied by subgroups. Compared to high-income countries (3/29, 10%), a higher proportion of low- and middle-income countries (4/24, 17%) prioritized safety. As the pandemic progressed, the duration of protection (2/24, 8%) during the pandemic wave and COVID-19 mortality risk (5/25, 20%) after the pandemic wave emerged as 2 of the most important attributes. Our review revealed the critical role of vaccine effectiveness and safety in COVID-19 vaccine preference. However, it should be noticed that preference heterogeneity was observed across subpopulations and may change over time. PROSPERO CRD42023422720; https://tinyurl.com/2etf7ny7.

An immunoinformatic investigation on Rift Valley fever virus protein reveals possible epitopes for vaccines.

This immunoinformatic study identified potential epitopes from the envelopment polyprotein (Gn/Gc) of Rift Valley fever virus (RVFV), a pathogenic virus causing severe fever in humans and livestock. Effective vaccination is crucial for controlling RVFV outbreaks. The identification of suitable epitopes is crucial for the development of safe and effective vaccines. Protein sequences were obtained from the UniProt database, and evaluated through VaxiJen v2.0 to predict the B and T-cell epitopes within the RVFV glycoprotein. Gn/Gc protein sequences were analyzed with bioinformatics tools and algorithms. The predicted T-cell and B-cell epitopes were evaluated for antigenicity, allergenicity, and toxicity by the VaxiJen v2.0 system, AllerTop v2.0, and ToxinPred server, respectively. We employed computational methods to screen the RVFV envelopment polyprotein encompassing N-terminal and C-terminal glycoprotein segments, to discover antigenic T- and B-cell epitopes. Our analysis unveiled multiple potential epitopes within the RVFV glycoprotein, specifically within the Gn/Gc protein sequences. Subsequently, we selected eleven cytotoxic T-lymphocytes (CTL) and four helper T-lymphocytes (HTL) for population coverage analysis, which collectively extended to cover 97.04% of the world's population, representing diverse ethnicities and regions. Notably, the CTL epitope VQADLTLMF exhibited binding affinity to numerous human leukocyte antigen (HLA) alleles. The identification of glycoprotein (Gn/Gc) epitopes through this immunoinformatic study bears significant implications for advancing the development of an effective RVFV vaccine. These findings provide valuable insights into the immunological aspects of the disease and may contribute towards the development of broad-spectrum antiviral therapies targeting other RNA viruses with similar polymerase enzymes.

Effects of adding antibiotics to an inactivated oil-adjuvant avian influenza vaccine on vaccine characteristics and chick health

During poultry immunization, antibiotics are typically added to inactivated oil-adjuvant avian influenza (AI) vaccines. Here, we evaluated the effects of adding ceftiofur, a third-generation cephalosporin, to an AI vaccine on vaccine stability and structure and on chick growth, immune efficacy, blood concentrations, biochemical and immunological indices, and gut microbiota. The results demonstrated that neither aqueous ceftiofur sodium nor ceftiofur hydrochloride oil emulsion formed a stable mixture with the vaccine. Adding ceftiofur formulations, particularly ceftiofur hydrochloride, at >4% significantly destabilized the vaccine's water-in-oil structures. Adding ceftiofur also increased vaccine malabsorption at the injection site; specifically, adding ceftiofur hydrochloride reduced H5N8 and H7N9 antibody titers after the first immunization (P < 0.05) and H7N9 antibody titers after the second immunization (P < 0.01). Serum drug concentrations did not differ significantly between the groups with ceftiofur sodium and hydrochloride addition. Ceftiofur addition increased postvaccination chick weight loss; compared with the vaccine alone, ceftiofur sodium-vaccine mixture increased chick weight significantly (P < 0.05). Ceftiofur addition also increased stress indices and reduced antioxidant capacity significantly (P < 0.05 or P < 0.01). Vaccination-related immune stress reduced gut microbiota diversity in chicks; ceftiofur addition reversed this change. AI vaccine immunization significantly reduced the relative abundance of Lactobacillus and Muribaculaceae but significantly increased that of Bacteroides and Eubacterium coprostanoligenes group. Ceftiofur addition restored the gut microbiota structure; in particular, ceftiofur hydrochloride addition significantly increased the abundance of the harmful gut microbes Escherichia-Shigella and Enterococcus, whereas ceftiofur sodium addition significantly reduced it. The changes in gut microbiota led to alterations in metabolic pathways related to membrane transport, amino acids, and carbohydrates. In conclusion, adding ceftiofur to the AI vaccine had positive effects on chick growth and gut microbiota modulation; however, different antibiotic concentrations and formulations may disrupt vaccine structure, possibly affecting vaccine safety and immunization efficacy. Thus, the addition of antibiotics to oil-adjuvant vaccines is associated with a risk of immunization failure and should be applied to poultry with caution.

Clinical presentation and symptomatology of Guillain-Barré syndrome: A literature review.

Guillain-Barré Syndrome (GBS) is a rare but potentially life-threatening neurological disorder characterized by acute onset ascending paralysis and sensory abnormalities. This article provides a comprehensive overview of GBS, covering its epidemiology, etiology, clinical presentation, diagnostic evaluation, management and treatment, prognosis, psychosocial impact, recent advances in research, public health implications, and ethical considerations. Epidemiological data reveal variations in GBS prevalence, incidence rates, and geographical distribution influenced by climate, infectious disease prevalence, and genetic susceptibility. Etiological factors include preceding infections, vaccinations, and autoimmune mechanisms, although the precise pathophysiology remains incomplete. Clinical presentation encompasses prodromal symptoms, motor deficits, sensory abnormalities, autonomic dysfunction, and variants such as Miller-Fisher Syndrome and Bickerstaff brainstem encephalitis. Neurological examination findings include weakness, paralysis, sensory deficits, and reflex changes, while autonomic dysfunction manifests as cardiovascular, respiratory, and gastrointestinal symptoms. Diagnostic evaluation relies on clinical criteria, laboratory tests (e.g., cerebrospinal fluid analysis, nerve conduction studies), and consideration of differential diagnoses. Management strategies encompass supportive care, immunomodulatory therapies (e.g., intravenous immunoglobulin, plasma exchange), and rehabilitation interventions to optimize functional outcomes and promote recovery. Prognosis varies depending on clinical features, treatment response, and complications such as respiratory failure and autonomic instability. Psychosocial impact encompasses psychological effects on patients and caregivers, highlighting the importance of coping strategies and support systems. Recent advances in research focus on emerging treatments, genetic predisposition, and biomarker discovery, offering promise for improving GBS outcomes. Public health implications include vaccination safety concerns and healthcare system considerations for GBS management. Ethical considerations encompass patient autonomy, resource allocation, and end-of-life decision-making.

Safety and immunogenicity of the live-attenuated hRVFV-4s vaccine against Rift Valley fever in healthy adults: a dose-escalation, placebo-controlled, first-in-human, phase 1 randomised clinical trial

Rift Valley fever virus, a pathogen to ruminants, camelids, and humans, is an emerging mosquito-borne bunyavirus currently endemic to Africa and the Arabian Peninsula. Although animals are primarily infected via mosquito bites, humans mainly become infected following contact with infected tissues or fluids of infected animals. There is an urgent need for adequate countermeasures, especially for humans, because effective therapeutics or vaccines are not yet available. Here we assessed the safety, tolerability, and immunogenicity of a next-generation, four-segmented, live-attenuated vaccine candidate, referred to as hRVFV-4s, in humans. A first-in-human, single-centre, randomised, double-blind, placebo-controlled trial was done in Belgium in which a single dose of hRVFV-4s was administered to healthy volunteers aged 18-45 years. Participants were randomly assigned using an interactive web response system. The study population encompassed 75 participants naive to Rift Valley fever virus infection, divided over three dosage groups (cohorts) of 25 participants each. All participants were followed up until 6 months. Using a staggered dose escalating approach, 20 individuals of each cohort were injected in the deltoid muscle of the non-dominant arm with either 104 (low dose), 105 (medium dose), or 106 (high dose) of 50% tissue culture infectious dose of hRVFV-4s as based on animal data, and five individuals per cohort received formulation buffer as a placebo. Primary outcome measures in the intention-to-treat population were adverse events and tolerability. Secondary outcome measures were vaccine-induced viraemia, vaccine virus shedding, Rift Valley fever virus nucleocapsid antibody responses (with ELISA), and neutralising antibody titres. Furthermore, exploratory objectives included the assessment of cellular immune responses by ELISpot. The trial was registered with the EU Clinical Trials Register, 2022-501460-17-00. Between August and December, 2022, all 75 participants were vaccinated. No serious adverse events or vaccine-related severe adverse events were reported. Pain at the injection site (51 [85%] of 60 participants) was most frequently reported as solicited local adverse event, and headache (28 [47%] of 60) and fatigue (28 [47%] of 60) as solicited systemic adverse events in the active group. No vaccine virus RNA was detected in any of the blood, saliva, urine, or semen samples. Rift Valley fever virus nucleocapsid antibody responses were detected in most participants who were vaccinated with hRVFV-4s (43 [72%] of 60 on day 14) irrespective of the administered dose. In contrast, a clear dose-response relationship was observed for neutralising antibodies on day 28 with four (20%) of 20 participants responding in the low-dose group, 13 (65%) of 20 responding in the medium-dose group, and all participants (20 [100%] of 20) responding in the high-dose group. Consistent with the antibody responses, cellular immune responses against the nucleocapsid protein were detected in all dose groups, whereas a more dose-dependent response was observed for the Gn and Gc surface glycoproteins. Neutralising antibody titres declined over time, whereas nucleocapsid antibody responses remained relatively stable for at least 6 months. The hRVFV-4s vaccine showed a high safety profile and excellent tolerability across all tested dose regimens, eliciting robust immune responses, particularly with the high-dose administration. The findings strongly support further clinical development of this candidate vaccine for human use. The Coalition for Epidemic Preparedness Innovations with support from the EU Horizon 2020 programme.

Efficacy and Immunogenicity of a Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine in Cynomolgus Macaques.

Filoviruses, like the Marburg (MARV) and Ebola (EBOV) viruses, have caused outbreaks associated with significant hemorrhagic morbidity and high fatality rates. Vaccines offer one of the best countermeasures for fatal infection, but to date only the EBOV vaccine has received FDA licensure. Given the limited cross protection between the EBOV vaccine and Marburg hemorrhagic fever (MHF), we analyzed the protective efficacy of a similar vaccine, rVSV-MARV, in the lethal cynomolgus macaque model. NHPs vaccinated with a single dose (as little as 1.6 × 107 pfu) of rVSV-MARV seroconverted to MARV G-protein prior to challenge on day 42. Vaccinemia was measured in all vaccinated primates, self-resolved by day 14 post vaccination. Importantly, all vaccinated NHPs survived lethal MARV challenge, and showed no significant alterations in key markers of morbid disease, including clinical signs, and certain hematological and clinical chemistry parameters. Further, apart from one primate (from which tissues were not collected and no causal link was established), no pathology associated with Marburg disease was observed in vaccinated animals. Taken together, rVSV-MARV is a safe and efficacious vaccine against MHF in cynomolgus macaques.

Delivery and Safety of a Two-Dose Preventive Ebola Virus Disease Vaccine in Pregnant and Non-Pregnant Participants during an Outbreak in the Democratic Republic of the Congo.

During the 2018-2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group.

FlagT4G Vaccine Prevents Transplacental Transmission of Highly Virulent Classical Swine Fever Virus after Single Vaccination in Pregnant Sows.

The transplacental transmission of CSFV and the resulting persistent congenital infection in newborn piglets have been abundantly discussed in pregnant sows suffering from virus infection. Importantly, the availability of safe commercial vaccines with proven efficacy to prevent the generation of congenital and postnatal persistent infections in pregnant sows are critical tools for controlling the disease in CSF endemic areas. Here, we demonstrate the high efficacy of a single dose of the recombinant FlagT4G vaccine to provide solid protection in pregnant sows against transplacental transmission of a highly virulent CSFV. Pregnant sows vaccinated with FlagT4G at 44 days of gestation elicited a strong CSFV-specific antibody response, with neutralizing antibody levels above those required for protection against CSFV. Importantly, after the challenge with a highly virulent CSFV, all foetuses from FlagT4G-vaccinated sows lacked CSF macroscopic lesions and showed a complete absence of the challenge virus in their internal organs at day 79 of gestation. Therefore, pregnant sows safely vaccinated with FlagT4G without affecting reproductive efficacy are efficaciously protected, along with their foetuses, against the infection and disease caused by a CSFV virulent field strain.

Validity and Reliability of the Greek Version of Adult Vaccine Hesitancy Scale in Terms of Dispositional Optimism in a Community-Dwelling Population: A Cross-Sectional Study.

Vaccine hesitancy is an important public health issue referring to concerns about the safety and efficacy of vaccination. Within a framework, this study aimed to assess the cultural adaptation, validity, and reliability of the Greek version of the adult Vaccine Hesitancy Scale (aVHS) as well as to identify the determinants of vaccine hesitancy among a large regional population in central Greece. A cross-sectional study was conducted enrolling 300 adults who had received primary healthcare services in the Health Centers and Local Health Units of the Magnesia Region from October to December 2022. The aVHS and the Life Orientation Test-Revised (LOT-R) were used to identify vaccine hesitancy and the dispositional level of optimism, respectively. For survey translation, the procedure of forward and backward translation was followed. Also, the aVHS was tested in a pilot study with a sample of 18 responders. Construct validity and internal consistency reliability were investigated via exploratory and confirmatory factor analysis and Cronbach's alpha coefficients, respectively. Simple and multiple linear regression analysis were used to determine predictors for vaccine hesitancy. Factor analyses indicated that the aVHS comprises two constructs ("lack of confidence" and "risk perception") explaining 68.9% of the total variance. The Cronbach's alpha of the total scale was 0.884, indicating its high internal consistency. Participants who lived in rural areas, had a lower annual income, and reported a lower level of optimism showed a higher lack of confidence in vaccination. On the other hand, people aged above 45 years old who had graduated from high school or elementary school and were unemployed showed greater aversion to the risks of side effects. Finally, certain socio-demographic characteristics were associated with vaccine hesitancy. Our data suggest that the aVHS is a valid and reliable instrument for measuring vaccine-related attitudes and perceptions in Greek society, providing meaningful insight into designing vaccination-related preventive interventions in the community.

Preliminary Evaluation of the Safety and Immunogenicity of a Novel Protein-Based Pneumococcal Vaccine in Healthy Adults Aged 18-49: A Phase Ia Randomized, Double Blind, Placebo-Controlled Clinical Study.

Background: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against Streptococcus pneumoniae and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). Methods: This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18-49 years. The participants were randomized into experimental (low-dose, medium-dose, high-dose) and placebo groups in a ratio of 3:1. Three doses of investigational vaccine were given to the participants with an interval of two months. Safety endpoints included the occurrence of total adverse reactions, solicited local and systemic adverse reactions, unsolicited adverse reactions, serious adverse events (SAEs), and several laboratory parameters. Immunogenicity endpoints included geometric mean titers (GMT) of anti-PspA (PRX1, P3296 and P5668) and anti-PlyLD antibodies level as determined by ELISA, seropositivity rates of PspA and PlyLD antibodies (>4-fold increase) and neutralization activity of anti-Ply antibody in serum. Results: A total of 118 participants completed the study of three doses. The candidate PBPV was safe and well-tolerated in all experimental groups. No vaccine-related SAEs were observed in this study. Most solicited adverse reactions were mild and transient. The most frequently reported solicited adverse reactions in the medium- and high-dose groups was pain at the injection site, while in the low-dose group it was elevated blood pressure. The immunogenicity data showed a sharp increase in the GMT level of anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies in serum. The results also showed that the elicited antibodies were dosage-dependent. The high-dose group showed a higher immune response against PspA-RX1, PspA-3296, PspA-5668, and PlyLD antigens. However, repeat vaccination did not increase the level of anti-PspA antibodies but the level of anti-PlyLD antibody. High seropositivity rates were also observed for anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies. In addition, a significant difference in the GMT levels of anti-Ply antibody between the high-, medium-, and low-dose groups post each vaccination were indicated by neutralization activity tests. Conclusions: The PBPV showed a safe and immunogenic profile in this clinical trial. Taking into consideration both safety and immunogenicity data, we propose a single dose of 50 µg (medium dose) of PBPV as the optimum approach in providing expanded protection against Streptococcus pneumoniae.

COVID-19 Vaccine Risk Perception and Associated Vaccine Hesitancy Among HIV-Infected People at Parirenyatwa Centre of Excellence

&amp;lt;i&amp;gt;Background:&amp;lt;/i&amp;gt; The impact of COVID-19 on people living with HIV (PLWH) is particularly concerning due to their existing health vulnerabilities. The low uptake of the COVID-19 vaccine and the failure to achieve herd immunity highlight the need to address vaccine hesitancy, especially in developing countries battling multiple infectious diseases. &amp;lt;i&amp;gt;Objective:&amp;lt;/i&amp;gt; This study aimed to determine the relationship between COVID-19 vaccine risk perception and vaccine hesitancy among PLWH. &amp;lt;i&amp;gt;Materials and Methods:&amp;lt;/i&amp;gt; An analytical cross-sectional design was used, involving 348 participants from Parirenyatwa Centre of Excellence, recruited via systematic random sampling. Data collection, following ethical approval, was conducted using a self-administered questionnaire. The data were categorized into structure, process, and outcome, and analyzed with SPSS version 22. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; The study found that 79.9% of PLWH perceived a risk in taking the COVID-19 vaccine. About 55% had moderate knowledge of COVID-19, and 48.4% of those vaccinated had completed the vaccine course, with 43.2% receiving two doses and 7.2% only one dose. Motivations for vaccination included accessing services, travel compliance, work allowances, and entry permissions. Vaccine hesitancy was evident in 56% of participants, who were also unlikely to recommend vaccination to others. A positive correlation (r=0.159, p&amp;lt;0.03) was observed between vaccine risk perception and hesitancy. Barriers included fear of long waits, vaccine safety concerns, and insufficient information. &amp;lt;i&amp;gt;Conclusions:&amp;lt;/i&amp;gt; The study demonstrated a significant positive correlation between vaccine risk perception and hesitancy among PLWH. It underscores the necessity of tailored vaccination messages addressing the specific concerns of PLWH and the need for increased governmental investment in awareness campaigns to achieve 75% herd immunity.

Closing the gaps in adolescent vaccinations: Rhode Island’s Vaccinate Before You Graduate program as a model for other jurisdictions

ObjectiveThe northeastern state of Rhode Island (RI) has a Vaccinate Before You Graduate (VBYG) program that supplements the traditional primary care infrastructure by providing vaccines to adolescents while they are in school, with no out-of-pocket expenses. We analyzed data from RI’s immunization registry to evaluate whether VBYG also reduces disparities in adolescent immunization rates. MethodsWe identified adolescent and catch-up vaccines administered in RI to people who were aged 11–18 at any point during the 5-year study period of 2019–2023, and conducted bivariate and multivariate analyses of vaccine administration data by setting (VBYG clinics, community health centers [CHCs], all other primary care practices [oPCPs], other school-based clinics, and other sites) and adolescent demographics (racial and ethnic identity, insurance status, sex, and age at time of vaccine). ResultsOf over 387,000 routine vaccines administered during the study period, 3.3 % were administered by a VBYG clinic despite significant declines during school closures associated with the early COVID-19 pandemic. VBYG-administered doses went to slightly older youth, and a higher proportion were catch-up doses (25.7 % versus 14.1 % for CHC doses and 6.5 % for oPCP). Youths received an average of 2.71 vaccines in VBYG clinics compared to 1.77 from oPCPs and 2.08 from CHCs. A higher proportion of vaccines administered by VBYG went to adolescents of color and those without private insurance than those administered by oPCPs. ConclusionsVBYG provides a model to other jurisdictions of a vaccine safety net for adolescents who may not otherwise receive recommended vaccines before exiting the school system.

Ocular Implications of COVID-19 Infection and Vaccine-Related Adverse Events.

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly impacted various organ systems, including the eyes. Initially considered a primarily respiratory disease, it is now evident that COVID-19 can induce a range of ocular symptoms. Recognizing these ocular manifestations is crucial for eye care practitioners as they can serve as early indicators of the disease. This review consolidates current evidence on the ocular effects of COVID-19, identifying manifestations such as conjunctivitis, scleritis, uveitis, and retinopathy. The increasing prevalence of these symptoms highlights the importance of thorough eye examinations and detailed patient histories in COVID-19 cases. Potential routes of viral entry into ocular tissues and the underlying mechanisms, including direct infection, immune responses, and vascular involvement, are explored. Additionally, this review addresses ocular side effects associated with COVID-19 vaccines, such as corneal graft rejection, uveitis, and retinal issues. These findings emphasize the need for ongoing surveillance and research to ensure vaccine safety.

Serosurveillance for Measles and Rubella.

Measles and rubella remain global health threats, despite the availability of safe and effective vaccines. Estimates of population immunity are crucial for achieving elimination goals and assessing the impact of vaccination programs, yet conducting well-designed serosurveys can be challenging, especially in resource-limited settings. In this review, we provide a comprehensive assessment of 130 measles and rubella studies published from January 2014 to January 2024. Methodologies and design aspects of serosurveys varied greatly, including sample size, assay type, and population demographics. Most studies utilized enzyme immunoassays for IgG detection. Sample sizes showed diverse sampling methods but favored convenience sampling despite its limitations. Studies spanned 59 countries, predominantly including adults, and revealed disparities in seroprevalence across demographics, regions, and notably among migrants and women. Age-related declines in antibodies were observed, particularly among infants, and correlations between vaccination status and seropositivity varied. We conclude with an outlook on measles and rubella serosurveillance, emphasizing the need for proper survey design and the advantages of standardized, multiplex serology assays.

Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques

Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.