Vaccine Safety Research Articles

Understanding vaccination behavior of healthcare workers in German hospitals-results from the OKaPII study

Influenza vaccination coverage in Germany is generally low. Even in hospitals, the demand for influenza vaccination is lacking although it has the potential to prevent the spread of the influenza virus and diseases. To take effective actions, adeeper understanding of vaccination behavior of healthcare workers is crucial. OKaPII is an annual German-wide online survey of clinical staff on influenza vaccination. Differences in vaccination behavior were tested for occupation, sex, and age, and differences in knowledge were tested between physicians and nurses. We used logistic regressions to analyze associations between psychological determinants and vaccination behavior among physicians and nursing staff. From 115 clinics, 15,312 employees participated in the survey (17 April to 15 May 2023). In the 2022/23 season, 58.7% of the participants were vaccinated against influenza. The vaccination coverage was 80.7% for physicians and 51.1% for nursing staff . The vaccination behavior of physicians and nursing staff was significantly associated with collective responsibility and confidence in vaccination safety. Of the knowledge items, 87.2% were answered correctly by physicians and 62% by nursing staff. We identified significant differences in vaccine uptake between occupational groups in German hospitals. Low vaccination coverage has existed for years, especially among nursing staff. Tailored interventions should promote the idea of protecting vulnerable people and confidence in the safety of vaccination. Increased education, especially on vaccination safety issues, can have apositive impact on the decision to vaccinate. Possibilities to get vaccinated despite time constraints in the workplace should be provided.

Immunogenicity and Safety According to Immunosuppressive Drugs and Different COVID-19 Vaccine Platforms in Immune-Mediated Disease: Data from SAFER Cohort

Background/Objectives: The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. Methods: The SAFER study: “Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease”, is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). Results: 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41–7.24), T2: 73.01 (61.53–86.62), T3: 200.0 (174.36–229.41) and T4: 904.92 (800.49–1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. Conclusions: All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies.

COVID-19 Vaccination and Transient Increase in CD4/CD8 Cell Counts in People with HIV: Evidence from China

Objectives: Accumulating evidence has confirmed the efficacy and safety of COVID-19 vaccines against SARS-CoV-2 infection. However, the effect of COVID-19 vaccination on immuno-virological parameters in people with HIV (PWH) is uncertain. Methods: A total of 372 PWH treated at Beijing Ditan Hospital were included. Unvaccinated PWH were matched 1:3 with vaccinated PWH using a propensity score matching algorithm. Differences in immuno-virological markers between the matched groups were analyzed. The Wilcoxon signed rank test was used to test for changes in CD4 and CD8 counts and HIV viral load over two months around vaccination. In addition, we investigated the long-term changes in HIV-related markers in different vaccination dose groups and in the entire vaccinated population. Results: Vaccinated PWH had a higher CD4/CD8 ratio (0.64 (0.49, 0.78) vs. 0.80 (0.56, 1.03), p = 0.037) than unvaccinated PWH within a two-month window after the third dose. There were 337 PWH who received COVID-19 vaccination, and 73.9% (n = 249) received three doses of vaccine. We observed a transient increase in CD4 count and CD4/CD8 ratio within a two-month window after vaccination, especially after the second dose (CD4 count: 583.5 (428.5, 706.8) vs. 618.0 (452.0, 744.0), p = 0.018; CD4/CD8 ratio: 0.70 (0.50, 0.91) vs. 0.71 (0.53, 0.96), p < 0.001)) and the third dose (CD4 count: 575.5 (435.5, 717.0) vs. 577.5 (440.8, 754.8), p = 0.001; CD4/CD8 ratio: 0.70 (0.52, 0.93) vs. 0.79 (0.53, 1.00), p < 0.001)). Recent CD4 counts and CD4/CD8 ratios were lower than after COVID-19 but remained higher than before COVID-19 in vaccinated PWH. In addition, COVID-19 vaccination had no negative effect on HIV viral load. Conclusions: A transient increase in CD4 count and CD4/CD8 ratio was observed after COVID-19 vaccination. However, the enhanced cellular immune response induced by vaccination may diminish over time and return to normal levels. There is no adverse effect of vaccination on HIV viral load.

Live attenuated goatpox vaccination in pregnant Murcia-Granada goats: dosage implications and outcomes

BackgroundInfectious diseases, particularly the Goatpox virus (GTPV) from the Poxviridae family, significantly impact livestock health and agricultural economies, especially in developing regions. Recent GTPV outbreaks in previously eradicated areas underscore the need for effective control measures, with vaccination being the most reliable strategy. This study investigates the effects of administering standard and double doses of live attenuated goatpox vaccine in pregnant Murcia-Granada goats, a non-native breed in Iran, to determine optimal vaccination protocols.ResultsIn 2018, 400 healthy and pregnant Murcia Granada goats imported from Spain were divided into groups of 200 and vaccinated with either a standard dose (0.5 ml) or a double dose (single 0.9 ml injection) of live attenuated goatpox vaccine. Post-vaccination, the goats were monitored daily for clinical signs of infection, with samples collected for PCR analysis to detect the presence of GTPV strains. In group A, which received the standard vaccine dose, no abortions or vaccine-related side effects were observed, and body temperatures remained normal. In group B, administered a double dose, 37% of the goats experienced abortions, displaying signs of GTPV infection, such as skin lesions (pox lesions) and increased body temperatures. Molecular analysis confirmed the vaccine strain of GTPV as the infection source, ruling out external contamination. Statistical analysis showed no significant differences in abortion rates concerning gestational age or t he age of the pregnant goats.ConclusionThe study highlights the importance of adhering to standard vaccine dosages in pregnant Murcia Granada goats to prevent adverse outcomes like abortions. This study emphasizes the necessity to review and revise vaccination protocols tailored to specific breeds and varying maintenance conditions, including pregnancy and outbreak scenarios. These findings stress the necessity for cautious and tailored vaccination strategies to ensure the safety and efficacy of vaccines in different goat breeds.

Prevalence and factors contributing to missed opportunities for vaccination in Mogadishu, Somalia

BackgroundVaccination is a critical public health intervention that significantly reduces morbidity and mortality from vaccine preventable diseases. Despite the proven benefits of vaccines, missed opportunities for vaccination (MOV) remain a significant challenge in many low-income countries, including Somalia. This study aimed to determine the prevalence and identify the factors contributing to MOV in Mogadishu, Somalia. MethodsA cross-sectional study was conducted at various healthcare facilities in Mogadishu, Somalia, from January to March 2024. A total of 234 caregivers of children under five years of age were interviewed using a structured questionnaire. Data on sociodemographic characteristics, health service utilization, and reasons for missed vaccinations were collected. Logistic regression analysis was used to identify factors associated with MOV. Results: The prevalence of MOV in Mogadishu was 26%. Key factors contributing to MOV included low socioeconomic status, lack of caregiver awareness about vaccination schedules, logistical challenges within the healthcare system, and misconceptions about vaccine safety and efficacy. Knowledge and beliefs of mothers about vaccination significantly affected the MOVs in children. Not knowing if all children should be vaccinated is associated with higher probability of (MOVs), (AOR =13.006, 95% CI = 1.175-143.924, p = 0.003). ConclusionThe study highlighted a significant prevalence of missed opportunities for vaccination in Mogadishu, Somalia. Addressing these missed opportunities requires a multifaceted approach, including enhancing public awareness about the importance of vaccination, improving healthcare infrastructure, and ensuring consistent vaccine supply and proper storage.

Participant-reported neurological events following immunization in the Canadian National Vaccine Safety Network-COVID-19 vaccine (CANVAS-COVID) study

IntroductionThe Canadian National Vaccine Safety Network (CANVAS) conducted active participant-based surveillance for adverse events following immunization during the COVID-19 vaccine campaign. This study evaluated the association between COVID-19 vaccination and neurological adverse events. MethodsParticipants were invited to complete online surveys to report health events that prevented daily activities and/or required medical attention within 7 days after COVID-19 vaccination or 7 days prior to the survey (unvaccinated controls); follow-up surveys were sent 7 months later. Neurological events were health events where the most severe symptom reported was ≥1 of: numbness/tingling, loss of taste or smell, vision loss, facial weakness/paralysis, seizure, weakness/paralysis of arms or legs, confusion, change in personality or behavior, or difficulty with urination or defecation. Data were extracted from the CANVAS-COVID database for analysis. ResultsCompleted survey responses were received from 15,273 unvaccinated controls, 758,619 dose 1 recipients, 406,884 dose 2 recipients, and 126,586 dose 3 recipients. Rates of neurological events ranged from 15.9 (95 % CI 13.6–18.4) per 10,000 dose 1 ChAdOx1 recipients to 8.4 (6.5–10.8) and 7.9 (5.7–11.0) per 10,000 dose 3 mRNA-1273 and BNT162b2 recipients, respectively. Multivariable regression adjusted for age, sex, previous SARS-CoV-2 infection, and baseline health status showed an increased risk of neurological event among ChAdOx1 dose 1 recipients versus controls (adjusted OR 2.3, 95 % CI 1.2–4.3), but not among mRNA vaccine recipients after any dose. Risk of anaesthesia/paresthesia were increased following ChAdOx1 dose 1 (aOR 4.7, 1.7–13.1), and consistently but not statistically significantly higher following any dose of either mRNA vaccine. Risk of loss of smell/taste was decreased among recipients of any dose of either mRNA vaccine versus controls. ConclusionsThe results support the safety of COVID-19 vaccines while confirming reported associations between ChAdOx1 dose 1 and neurological events. Participant-based AEFI surveillance is a useful component of post-market surveillance programs.

Safety and immunogenicity of the yellow fever vaccine for patients with end-stage renal disease

Resumo Introdução: Em dezembro de 2016, houve um surto de febre amarela (FA) silvestre em áreas não endêmicas da região sudeste do Brasil. A resposta imunológica à vacina contra FA e sua segurança em indivíduos com doença renal crônica (DRC) que vivem em regiões endêmicas de febre amarela não são totalmente compreendidas. O objetivo deste estudo foi avaliar a incidência de eventos adversos e a resposta sorológica após vacinação primária com a vacina 17DD-YF em pacientes com DRC submetidos à diálise. Métodos: Este foi um estudo de coorte retrospectivo e multicêntrico envolvendo 223 indivíduos com DRC que estavam em diálise após vacinação primária contra FA. Foram coletadas características clínicas, epidemiológicas e avaliados os eventos adversos da vacina (EAV). Cerca de 35 meses após a vacinação, a resposta sorológica foi avaliada em 71 (32%) pacientes usando testes de neutralização. Resultados: Não houve EAV grave em nenhum paciente. Reações locais foram relatadas em 13 indivíduos (5,8%), enquanto 6 (2,7%) relataram reações sistêmicas generalizadas e 205 (91,9%) não apresentaram nenhum EAV. Nenhuma característica clínica ou epidemiológica predisse a ocorrência de EAV. Uma resposta sorológica adequada foi encontrada em 38% dos participantes e nenhuma das características clínicas ou epidemiológicas foi associada à imunogenicidade. Conclusão: Os desfechos de nosso estudo sugerem que a vacina contra FA é bem tolerada em pacientes com DRC em diálise, mas não induz uma resposta imunológica adequada. Pesquisas futuras devem se concentrar na avaliação das respostas imunes tanto celulares quanto humorais após a administração de várias doses da vacina contra FA.

Safety and immunogenicity of the yellow fever vaccine for patients with end-stage renal disease.

In December 2016, an outbreak of sylvatic yellow fever (YF) occurred in the non-endemic areas of the south-eastern region of Brazil. The immune response to the yellow fever vaccine and its safety in individuals with chronic kidney disease (CKD) living in YF-endemic regions are not thoroughly understood. The objective of this study is to assess the incidence of adverse events and the serological response after primary vaccination with the 17DD-YF vaccine in CKD patients undergoing dialysis. This was a multicenter, retrospective cohort study involving 223 individuals with CKD who were on dialysis after primary vaccination against YF. Clinical and epidemiologic characteristics were collected and the vaccine adverse event (VAE) were assessed. Around 35 months after vaccination, the serological response was evaluated in 71 (32%) patients using neutralization tests. No serious VAE occurred in any patient. Local reactions were reported in 13 individuals (5.8%), while 6 (2.7%) reported generalized systemic reactions and 205 (91.9%) did not display any VAE. No clinical or epidemiologic characteristic predicted the occurrence of VAE. Adequate serological response was found in 38% of participants and none of the clinical or epidemiological characteristics were associated with immunogenicity. The outcomes of our study suggest that the yellow YF vaccine is well-tolerated in CKD patients undergoing dialysis, but it does not induce adequate immune response. Future research should focus on evaluating both cellular and humoral immune responses following administration of various doses of the YF vaccine.

Safety and Effectiveness of the Pfizer-BioNTech COVID-19 Vaccine among Health Staff in Sulaimani City, Iraq: A Prospective Cohort Study

A cohort study was conducted among 210 health staff members in Sulaimani city to assess the safety and effectiveness of the Pfizer-BioNTech vaccine. They were divided into two groups: vaccinated and unvaccinated. The vaccinated group received two doses of the Pfizer vaccine, while the unvaccinated group did not receive any vaccines during this study. Vaccine reactogenicity was assessed using a self-report form. Whereas vaccine immunogenicity was assessed by testing the anti-receptor binding domain IgG (anti-RBD IgG) antibody. Several adverse effects were observed with each dose. The most frequent adverse effects were pain at the inoculation site, tiredness, myalgia and fever. The average adverse effects per person in the first and second doses were 5.3 (SD 3.3) and 6.3 (SD 3.5) respectively (p = 0.005). The immunized group's anti-RBD IgG antibody levels were greatly improved after taking the first and second doses (32.50 and 44.92 binding antibody units (BAU)/mL respectively). After eight months of taking the two doses, the antibody level dropped to 17.00 BAU/mL. This study indicates that the vaccine can be safe and effective for enhancing antibody production.

Vaccination in hemophilic children: Challenges, innovations, and future directions

Introduction: Hemophilia, an inherited disorder primarily affecting blood clotting due to deficiencies in clotting factors VIII or IX, presents complex challenges for vaccination. Children with hemophilia require vaccinations to prevent infections that may exacerbate their bleeding disorder. However, traditional intramuscular vaccination poses bleeding risks, necessitating specialized administration methods and careful post-vaccination care. Purpose: This study examines the efficacy and safety of vaccination in pediatric hemophilia patients, emphasizing the importance of individualized protocols to manage bleeding risks effectively. It explores recent advancements, including needle-free technologies, the potential of gene therapy, and mRNA vaccines. Materials and Methods: The study synthesizes current guidelines from global health organizations, hemophilia management protocols, and clinical studies on vaccine safety in hemophilia. It highlights techniques such as subcutaneous administration, clotting factor prophylaxis, and the use of fine-gauge needles to minimize bleeding complications. Results: Findings indicate that with appropriate management, hemophilic children achieve adequate immune responses to vaccines, with reduced bleeding risks. Emerging technologies, such as microneedle patches, jet injectors, and gene therapy, offer promising safer vaccination alternatives. Additionally, mRNA vaccines demonstrate strong immunogenicity without the need for live-virus vectors, reducing complication risks. Conclusions: Vaccination, when adapted to hemophilia-specific needs, remains essential for infection prevention in this vulnerable population. Newer vaccine technologies and individualized care protocols enhance safety and efficacy, contributing to improved quality of life and long-term health outcomes for hemophilic children.

The Role of Law in Regulating Compulsory Vaccination: Between Human Rights and State Obligations during the Pandemic

Public health protection is one of the main obligations of the state in an effort to maintain the welfare of its citizens. One of the policies implemented is mandatory vaccination to reduce the spread of infectious diseases and maintain collective health. However, this policy raises challenges in terms of balancing between the state's responsibility to protect the community and individual human rights, especially the right to determine which medical interventions to accept. This research aims to examine the role of law in regulating mandatory vaccination in Indonesia, as well as how the policy can be implemented without violating human rights. This study uses a normative juridical approach by exploring various regulations that form the basis for the implementation of mandatory vaccination in Indonesia, including Law Number 36 of 2009 concerning Health and Presidential Regulation Number 99 of 2020 concerning Vaccine Procurement and Vaccination Implementation. The analysis shows that compulsory vaccination has a strong legal footing to protect public health, but it must still respect individual rights, especially the right to choose medical interventions. The state is also required to ensure that this policy is implemented in a fair and non-discriminatory manner, especially for vulnerable groups such as children, the elderly, and individuals with special health conditions. This study also found that adequate education and socialization are important factors to increase public acceptance of mandatory vaccination. Public opposition is generally caused by a lack of proper understanding of the benefits of vaccines, as well as the spread of inaccurate information about vaccine safety. Therefore, a more persuasive approach, involving community leaders and related institutions, is needed to provide better understanding and increase public trust in vaccination policies. Mandatory vaccination policies need to be implemented while maintaining a balance between the state's obligation to protect public health and human rights. Not only does the state need to strengthen the legal basis for vaccination, but it must also ensure that this policy is implemented in a fair and inclusive manner.

Evaluating the efficacy and safety of the Covishield vaccine: Balancing immune response and side effects in diverse populations

Evaluating the efficacy and safety of the Covishield vaccine: Balancing immune response and side effects in diverse populations

Risk of canine distemper virus vaccination of domestic dogs in giant panda habitat to giant pandas

The giant panda (Ailuropioda melanoleuca), a unique relic species in China and a global biodiversity conservation symbol, faces the threat of canine distemper virus (CDV). Vaccinating domestic dogs in panda habitats against CDV is crucial, yet the associated risks remain understudied. We investigated the safety of CDV vaccination in 69 domestic dogs within panda habitats, employing enzyme-linked immunosorbent assay for CDV antibodies and quantitative reverse transcription polymerase chain reaction for viral RNA, a marker of viral shedding. Results revealed that vaccinated dogs posed a risk through viral shedding, mainly starting from the ninth day post-vaccination. Unvaccinated dogs exhibited increased CDV antibodies and subsequent shedding, with phylogenetic analysis confirming infection from vaccinated dogs in shared kennels. Dogs with higher initial antibodies displayed reduced shedding and a markedly abbreviated shedding duration (6.7 days) than those with lower initial antibodies (9.8 days). Habitat area analysis revealed substantial overlaps between domestic dogs and wild giant pandas in two nature reserves in China. To safeguard wildlife, particularly giant pandas, we recommend restricting vaccinated dogs’ activity for at least three weeks post-vaccination, complementing existing management practices. We advocate collaborative efforts among local authorities, reserve management and villagers for effective vaccination and post-vaccination management of domestic dogs.

PERSISTENT COAGULATION ABNORMALITIES IN RECOVERED COVID-19 PATIENTS FOLLOWING VACCINATION: A RETROSPECTIVE ANALYSIS

This retrospective observational study assessed persistent coagulation abnormalities in individuals who recovered from COVID-19 and subsequently received two doses of COVID-19 vaccination. The study enrolled 250 individuals, aged 20–50 years, and evaluated four primary coagulation markers: prothrombin time, activated partial thromboplastin time, D-dimer, and fibrinogen. Blood samples were analyzed using the STA-R coagulation analyzer. Results indicated that 10% of participants exhibited elevated D-dimer levels, 34% had elevated prothrombin times, and 85% displayed prolonged activated partial thromboplastin times, while 7.2% showed increased fibrinogen levels. Statistical analysis revealed significant deviations in D-dimer, activated partial thromboplastin time, and fibrinogen from standard reference ranges. These abnormalities suggest a possible hypercoagulable state post-vaccination, potentially due to vaccine-induced mechanisms that activate coagulation pathways. Findings align with reports of vaccine-induced thrombotic complications, especially in adenovirus-vectored vaccines. This study underscores the importance of monitoring coagulation parameters in vaccinated individuals with prior COVID-19 infection to ensure vaccine safety and efficacy. Future studies should investigate the underlying mechanisms of these coagulation changes and their clinical implications.

Determinants of COVID-19 Vaccine Acceptance and Hesitancy: A Systematic Review

Background/Objectives: COVID-19 is an infectious disease whose prevention is significantly aided by vaccination, which reduces both case severity and mortality. Despite the safety and efficacy of vaccines, acceptance is not universal, and understanding of the factors influencing vaccination decisions and hesitancy remains limited. This review aims to identify and analyze studies addressing two key questions: what influences the decision to vaccinate and what factors are associated with vaccine hesitancy. Methods: This systematic review was conducted following the PRISMA guidelines. Data collection utilized descriptors related to vaccine adherence and hesitancy, based on the PEO strategy of the Joanna Briggs Institute (JBI). Searches were conducted in Embase, Scopus, PubMed, Lilacs, and Web of Science, focusing on publications from 2021, the year the first COVID-19 vaccine was approved. After excluding duplicates and selecting articles based on eligibility criteria, the analysis involved data extraction and methodological quality assessment using JBI tools. Results: A total of 5268 publications were identified, with 30 included in this study. Factors associated with vaccine hesitancy included low education levels, social media influence, confidence in vaccine safety, and fear of side effects. In contrast, factors linked to vaccine acceptance included higher education, higher income, older age, and existing comorbidities. Conclusions: The findings highlight the urgent need for targeted health communication and education strategies, particularly for vulnerable groups. Public health policies should incorporate these factors to enhance vaccination adherence and build public confidence in vaccine safety, which is essential for mitigating future health emergencies.

Investigating parental perceptions of respiratory syncytial virus (RSV) and attitudes to RSV vaccine in Jiangsu, China: Insights from a cross-section study

IntroductionOur study aimed to assess parents' perceptions of respiratory syncytial virus (RSV) and their attitudes towards the RSV vaccine in China. MethodThe cross-section study was performed between August 21 and November 15, 2023, in Jiangsu province, eastern China. We collected socio-demographics, awareness, knowledge, perceptions of susceptibility and severity of RSV, and attitudes towards RSV vaccine using online survey questionnaire from parents of child aged ≤14 years old. The chi-square test and logistic regression model to explore the associated factors. ResultsA total of 2135 participants were included. About 26.0 % indicated that they had never heard of RSV (556/2135) and were unaware that infants and young children are at a high risk of contracting RSV (557/2135). The proportion of parents with a child under 1 year of age who were unaware of RSV was notably higher than that of parents with children in other age groups. 42.9 % of parents (916/2135) showed low level of perceived susceptibility of contacting RSV infection for their child. 70.6 % of parents (1508/2135) expressed their willingness to vaccinate their child against RSV. The most common reason for refusing the RSV vaccine was “Concern about vaccine's safety or side effects.” 60.8 % of participants (1299/2135) considered a price of the RSV vaccine below 200 CNY (28 USD) as acceptable. ConclusionThe parents, particularly those with younger children, exhibited limited awareness and knowledge regarding RSV infection. Our study also showed the potential role of vaccine price as a barrier to the future use of RSV vaccine in China.

Assessment of Placental Antioxidant Defense Markers in Vaccinated and Unvaccinated COVID-19 Third-Trimester Pregnancies

Background: Pregnancy has been identified as a risk factor for severe COVID-19, leading to maternal and neonatal complications. The safety and effects of the SARS-CoV-2 vaccination during pregnancy, particularly on placental function and oxidative stress (OxS), remain underexplored. We investigated the impact of vaccination on third-trimester placental antioxidant defense markers. Methods: Ninety full-term pregnant women were divided into the following groups: vaccinated (n = 27) and unvaccinated (n = 25) COVID-19-positive pregnant women; control subgroups were composed of vaccinated (n = 19) or unvaccinated (n = 19) COVID-19-negative women with a healthy term singleton pregnancy with no signs of COVID-19. Placental samples were collected after delivery. Lipid peroxidation (TBARS), gene expression of HIF-1α, and catalase (CAT), superoxide dismutase-1 (SOD1) and CAT-SOD1 enzymatic activity were measured. Results: COVID-19-positive placentae exhibited significantly higher TBARS and HIF-1α levels compared to controls, regardless of vaccination status. Vaccination significantly increased placental CAT and SOD1 expression and activity in COVID-19-positive women, suggesting enhanced antioxidant defense. Unvaccinated women showed a higher incidence of COVID-19 symptoms and lower antioxidant enzyme activity. Conclusions: SARS-CoV-2 infection induced placental OxS, which is countered by a placental adaptive antioxidant response. Vaccination during pregnancy enhances placental defense, further supporting the safety and benefits of COVID-19 vaccination in preventing complications and protecting fetal development.

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: A randomised, comparator-controlled, phase 2 trial

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and lower-middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A public sector manufacturer in Vietnam assessed the immunogenicity of NDV-HXP-S (COVIVAC) relative to an authorized vaccine. This phase 2 stage of a randomised, observer-blind, controlled, phase 1/2 trial was conducted at three community health centers in Thai Binh Province, Vietnam. Healthy males and non-pregnant females, 18years of age and older, were eligible. Participants were randomised by age (18-59, ≥60years) to receive one of three treatments by intramuscular injection twice, 28days apart: COVIVAC at 3μg or 6μg, or AstraZeneca COVID-19 vaccine VAXZEVRIA™. Participants and personnel assessing outcomes were masked to treatment. The vaccine dose was selected based on Phase 1 results. A 6μg dose was chosen to explore the immunogenicity gain over the 3-μg dose. The study's aim is to evaluate the safety and immunogenicity of COVIVAC at two dose levels compared to VAXZEVRIA, the most commonly used COVID-19 vaccine in Vietnam. The main outcome was the induction of 50% neutralising antibody titers against vaccine-homologous pseudotyped virus 14days (day 43) and 6months (day 197) after the second vaccination by age group. The primary immunogenicity and safety analyses included all participants who received one dose of the vaccine. ClinicalTrials.govNCT05940194. During August 10-23, 2021, 737 individuals were screened, and 374 were randomised (124-125 per group); all subjects received vaccine dose one and all but three received doses two four weeks later. Subjects 18-59years of age achieved the following geometric mean titers of PNA 14days after vaccine dose two: 153⋅28 (95 % CI 124·2-189⋅15) for COVIVAC 3μg, 176⋅2 (95 % CI 141⋅45-220.27) for COVIVAC 6μg, and 99⋅92(95 % CI 80.80-123⋅56) for VAXZEVRIA. Subjects ≥60years of age also achieved potent geometric mean titers of PNA at the same timepoint: 183⋅57 (95 % CI 133.4-252⋅61) for COVIVAC 3μg, 257⋅87 (95 % CI 181⋅6-367⋅18) for COVIVAC 6μg, and 79⋅49(95 % CI 55⋅68-113⋅4) for VAXZEVRIA. On day 43, the geometric mean fold rise of 50% neutralising antibody titers for subjects age 18-59years was 31·20 (COVIVAC 3μgN=82, 95 % CI 25·14-38·74), 35·80 (COVIVAC 6μg; N=83, 95 % CI 29·03-44·15), 18·85 (VAXZEVRIA; N=82, 95 % CI 15·10-23·54), and for subjects age≥60years was 37·27 (COVIVAC 3μg; N=42, 95% CI 27·43-50·63), 50·10 (COVIVAC 6μg; N=40, 95% CI 35·46-70·76), 16·11 (VAXZEVRIA; N=40, 95 % CI 11·73-22·13). Among subjects seronegative for anti-S IgG at baseline, the day 43 geometric mean titer ratio of neutralising antibody (COVIVC 6μg/VAXZEVRIA) was 1·77 (95 % CI 1·30-2·40) for subjects age 18-59years and 3·24 (95% CI 1·98-5·32) for subjects age≥60years. On day 197, the age-specific ratios were 1·11 (95% CI 0·51-2·43) and 2·32 (0·69-7·85). Vaccines were well tolerated; reactogenicity was predominantly mild and transient. The percentage of subjects with unsolicited adverse events (AEs) during 28days after vaccinations was similar among treatments (COVIVAC 3μg 29·0%, COVIVAC 6μg 23·2%, VAXZEVRIA 31·2%); no vaccine-related AE was reported. Considering that induction of neutralising antibodies against SARS-CoV-2 has been correlated with the efficacy of COVID-19 vaccines, including VAXZEVRIA, our results suggest that vaccination with COVIVAC may afford clinical benefit matching or exceeding that of the VAXZEVRIA vaccine. ClinicalTrials.govNCT05940194.

A novel pan-epitope based nanovaccine self-assembled with CpG enhances immune responses against flavivirus

BackgroundFlavivirus is a highly prevalent and outbreak-prone disease, affecting billions of individuals annually and posing substantial public health challenges. Vaccination is critical to reducing the global impact of flavivirus infections, making the development of a safe and effective vaccine a top priority. The self-assembled pan-epitope vaccine presents key advantages for improving immunogenicity and safety without relying on external vectors or adding immunomodulatory elements, both of which are essential for successful vaccine development.ResultsIn this study, the pan-epitope peptide TBT was combined with adjuvant CpG to form the TBT-CpG nanovaccine (TBT-CpG NaVs), which was found to be spherical, uniform in shape, and demonstrated strong serum stability. In vitro studies showed that the TBT-CpG NaVs were efficiently taken up and internalized by bone marrow-derived dendritic cells (BMDCs). Flow cytometry and transcriptomic analysis indicated that the antigens were effectively presented to antigen-presenting cells (APCs) via the MHC II pathway, which facilitated BMDCs maturation and promoted the release of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. In vivo studies confirmed that TBT-CpG NaVs enhanced antigen-specific IgG levels, significantly increased IFN-γ and IL-4 expression in spleen cells, and offered protective effects against Dengue virus (DENV) and Zika virus (ZIKV) infections. Safety evaluations revealed no hepatotoxicity and no significant organ damage in immunized mice.ConclusionThe self-assembled candidate nanovaccine TBT-CpG NaVs effectively activates BMDCs and triggers a targeted immune response, providing antiviral effects against DENV and ZIKV. This vaccine demonstrates good immunogenicity and safety, establishing a promising foundation and a new strategy for the development of safe and effective vaccines.Graphical

Intralesional Bacillus-Calmette-Guerin (BCG) vaccine for multiple non-genital viral warts

Background: The majority of treatment options available for warts are destructive with some limitations to their utility, especially in the setting of multiple lesions. Accordingly, there is a need for other treatment options. Immunotherapy is a promising method for such cases. Intralesional administration of Bacille Calmette-Guerin (BCG) vaccine is one of the immunotherapeutic methods. It was intended to display the results of BCG immunotherapy in the treatment of multiple non- genital warts in a group of patients at Al-Karak Government Hospital. Objective: To evaluate the efficacy and safety of intralesional BCG vaccine in the treatment of non-genital multiple warts in a group of our patients at Al-Karak Government Hospital. Methods: A total number of 15 immunocompetent patients with non-genital multiple warts, with an age range of (12-39) years were included. Intralesional BCG vaccine was injected into the largest wart at 0, 4 and 8 weeks. Patients were followed up every 4 weeks for a total of 6 months Results: Complete response was noted in 12 patients after 4-16 weeks of the first injection, while 3 cases displayed a partial response. Few local and transient reaction were seen. No serious side effects were encountered. Limitations: The results are based on a small sample size (15 cases) and there was no control group for comparison. Conclusion: Immunotherapy with intralesional BCG vaccine is an effective and safe treatment option for immunocompetent patients with non-genital multiple warts.