Vaccine Safety Research Articles

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to

With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

BECC-engineered live-attenuated Shigella vaccine candidates display reduced endotoxicity with robust immunogenicity in mice.

Shigella spp. infection contributes significantly to the global disease burden, primarily affecting young children in developing countries. Currently, there are no FDA-approved vaccines against Shigella, and the prevalence of antibiotic resistance is increasing, making therapeutic options limited. Live-attenuated vaccine strains WRSs2 (S. sonnei) and WRSf2G12 (S. flexneri 2a) are highly immunogenic, making them promising vaccine candidates, but possess an inflammatory lipid A structure on their lipopolysaccharide (LPS; also known as endotoxin). Here, we utilized bacterial enzymatic combinatorial chemistry (BECC) to ectopically express lipid A modifying enzymes in WRSs2 and WRSf2G12, as well as their respective wild-type strains, generating targeted lipid A modifications across the Shigella backgrounds. Dephosphorylation of lipid A, rather than deacylation, reduced LPS-induced TLR4 signaling in vitro and dampened endotoxic effects in vivo. These BECC-modified vaccine strains retained the phenotypic traits of their parental strains, such as invasion of epithelial cells and immunogenicity in mice without adverse endotoxicity. Overall, our observations suggest that BECC-engineered live attenuated vaccines are a promising approach to safe and effective Shigella vaccines.

COVID-19 vaccine acceptance and associated factors among pregnant and lactating women attending maternity care clinics in refugee camps in Jordan.

Despite the advantages of vaccination in preventing maternal and fetal problems, there were many concerns in the medical community regarding vaccine safety for pregnant women, and this has put obstetricians in a challenging situation when it comes to advising their pregnant patients on whether to obtain the vaccine. This study was performed to define the level of acceptance of COVID-19 vaccination and assess the impact of COVID-19 attitudes and knowledge on vaccine acceptance between pregnant and lactating Syrian women who are seeking prenatal care services at the clinics in Azraq refugee camp in Jordan. A quantitative, cross-sectional study utilizing a non-probability convenience sample. A validated and reliable self-administered questionnaire consisting of four sections was used. A total of 412 pregnant/lactating women was recruited The acceptance rate of the COVID-19 vaccine among participants was 86.5%. There was a significant positive moderate association between respondents' attitudes and knowledge around the COVID-19 vaccine and their acceptance of the vaccine (r = .468, p < .001, r = .357, p < .001), respectively. To effectively mitigate the COVID-19 pandemic and achieve collective protection, decision-makers must intensify the efforts in promoting the importance of maternal vaccination, especially in vulnerable communities that suffer the most from pandemic outcomes.

Safety Assessment of Co-Administered SARS-CoV-2 Vaccines in BALB/c Mice

The onset of Coronavirus disease 2019 (COVID-19) in late 2019 presented a severe worldwide health crisis with widespread morbidity and mortality. Various vaccine platforms have been rapidly developed and approved for broad use in a swift and urgent response to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines differ significantly in terms of safety. Heterologous prime-boost vaccination enhances vaccine safety compared to homologous vaccination, although it could lead to a higher cumulative number of transient adverse events reported at each visit. Therefore, additional strategies are necessary to improve SARS- CoV-2 vaccine safety. Anecdotal options suggest that vaccine co-administration can significantly reduce these adverse effects and consequently, avert the need for frequent booster doses. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the safety profiles of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored and inactivated vaccines. Twenty-eight days post-immunization, safety profiles of the various treatments were evaluated through hematological and biochemical examination. Importantly, the co-administration regimens proved safe and were well-tolerated in mice, as evidenced by the normal hematological and biochemical values.

Global and regional burden of vaccine-induced thrombotic thrombocytopenia, 1969-2023: Comprehensive findings with critical analysis of the international pharmacovigilance database.

The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

BackgroundImmunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination.MethodsWe analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest.ResultsOverall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions.ConclusionsCOVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Immunogenicity and safety of a self-assembling ZIKV nanoparticle vaccine in mice

Zika virus (ZIKV) is a mosquito-borne flavivirus that highly susceptibly causes Guillain-Barré syndrome and microcephaly in newborns. Vaccination is one of the most effective measures for preventing infectious diseases. However, there is currently no approved vaccine to prevent ZIKV infection. Here, we developed nanoparticle (NP) vaccines by covalently conjugating self-assembled 24-subunit ferritin to the envelope structural protein subunit of ZIKV to achieve antigen polyaggregation. The immunogenicityof the NP vaccine was evaluated in mice. Compared to monomer vaccines, the NP vaccine achieved effective antigen presentation, promoted the differentiation of follicular T helper cells in lymph nodes, and induced significantly greater antigen-specific humoral and cellular immune responses. Moreover, the NP vaccine enhanced high-affinity antigen-specific IgG antibody levels, increased secretion of the cytokines IL-4 and IFN-γ by splenocytes, significantly activated T/B lymphocytes, and improved the generation of memory T/B cells. In addition, no significant adverse reactions occurred when NP vaccine was combined with adjuvants. Overall, ferritin-based NP vaccines are safe and effective ZIKV vaccine candidates.

Safety and efficacy of C. muridarum vaccines adjuvanted with CpG-1826 and four concentrations of Montanide-ISA-720-VG

It is recommended that the adjuvant Montanide ISA 720 VG be used at a concentration of 70% v/v. At this concentration, Montanide causes at the site of immunization a local granuloma that can last for several weeks. To determine the safety and protective efficacy of a Chlamydia muridarum MOMP vaccine, formulated with CpG-1826 and four different concentrations of Montanide (70%, 50%, 30% and 10%), BALB/c (H-2d) female mice were immunized twice intramuscularly. Local reactogenicity was significant for vaccines formulated with 70% or 50% Montanide but not for those inoculated with 30% or 10% Montanide. Robust humoral and cell mediated memory immune responses were elicited by the 70%, 50% and 30% Montanide formulations. Mice were challenged intranasally with 104 C. muridarum inclusion forming units (IFU). Based on changes in body weight, lungs’s weight and number of IFU recovered, mice vaccinated with the 70%, 50% and 30% Montanide formulations were significantly protected, but not mice receiving 10% Montanide. To conclude, we recommend the 30% Montanide concentration to be tested in humans and animal models to determine its safety and efficacy, in comparison to the 70% Montanide concentration currently used. The 30% Montanide formulation could significantly facilitate licensing of this adjuvant for human use.

Protein Nanoparticles as Vaccine Platforms for Human and Zoonotic Viruses.

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterisation of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs, have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from human viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious viral diseases and enhancing vaccine efficacy and safety.

Influenza Vaccine Hesitancy among Cancer Survivors in China: A Multicenter Survey.

Cancer survivors are at higher risk of developing severe complications from influenza due to their compromised immune systems. Despite their increased vulnerability to influenza and the availability of vaccines, vaccine hesitancy among cancer survivors remains a significant public health concern in China. A multicenter, cross-sectional study was conducted among cancer survivors in China from January to December 2023. A total of 500 participants were recruited from the oncology departments of five tertiary hospitals. A structured, self-administered questionnaire was used to collect data on socio-demographic characteristics, cancer-related information, medical history, lifestyle factors, and influenza vaccine hesitancy. Univariate and multivariate logistic regression analyses were performed to identify factors associated with influenza vaccine hesitancy. The response rate was 97.0% (485/500). Among all participants, 204 (42.06%) reported vaccine hesitancy. The results of multiple logistic regression showed that the longer the end of anti-cancer treatment, without a history of adverse vaccine reactions, and the level of family support played a protective role in vaccine hesitancy. Current rehabilitation status, frequent colds, not being informed by doctors about vaccination, exercising, lack of community vaccination education programs, and concerns about vaccine safety were risk factors that increase vaccine hesitancy. A high proportion of cancer survivors in our study reported influenza vaccine hesitancy. Addressing concerns about vaccine safety, improving access to vaccination services, and enhancing doctor-patient communication are crucial for increasing influenza vaccine uptake in this vulnerable population.

Engaging Trusted Messengers to Increase COVID-19 Pediatric Vaccine Uptake in Philadelphia: Lessons from the VaxUpPhillyFamilies program

IntroductionCommunities of color had higher rates of Coronavirus (COVID-19) infection and lower rates of COVID-19 vaccination during the pandemic. Parental concern about the safety and necessity of pediatric COVID-19 vaccines contribute to low childhood vaccination. Enlisting parents and caregivers as trusted messengers is an evidence-based approach to mitigate this challenge. VaxUpPhillyFamilies was formed to engage parents and caregivers as vaccine ambassadors to increase vaccination rates in children of color. This study aimed to understand the key benefits, challenges, and lessons learned from the VaxUpPhillyFamilies program. MethodsThree online debriefing sessions with ambassadors were conducted between September 7 and October 24, 2022, to share best practices, address challenges, receive emerging vaccine information, and provide support. Thematic analysis was utilized to develop broad themes and subthemes. ResultsFour themes with corresponding subthemes were identified: 1) Motivations to Become an Ambassador: a) improving the health of the community and b) personal satisfaction; 2) Defining Success: a) community interactions and b) influencing opinions; 3) Best Approaches: a) being mentally prepared with facts, b) addressing community health needs beyond COVID-19, c) demonstrating empathy, d) “meeting them where they’re at” by motivational interviewing, and e) building trust and connection; 4) Challenges: a) changes in vaccine guidelines, b) vaccine misinformation, c) varied perceptions of severity of COVID-19 illness and benefits of the vaccine, d) breakdown of communication from trusted sources, and e) structural barriers to engagement. ConclusionParents and caregivers were a resource for delivering evidence-based messaging about COVID-19 and other health challenges. To effectively equip parents and caregivers as public health ambassadors, it is critical to offer training in engagement strategies, to identify and combat misinformation, and to provide support in navigating challenges. VaxUpPhillyFamilies program is a model for future public health campaigns.

A Comprehensive Review on Rubella Virus

Rubella, colloquially known as German measles, is an exceptionally contagious viral illness that primarily affects children and non-immune young adults. While the infection is typically mild and self-limiting in most cases, rubella virus infection during early pregnancy can have devastating consequences, leading to a range of severe birth defects collectively termed congenital rubella syndrome (CRS). The etiological agent, Rubella virus (RV), is an enveloped, positive-sense single-stranded RNA virus and the sole member of the genus Rubivirus within the Matonaviridae family. Despite the availability of an effective and safe rubella vaccine, the disease continues to pose a significant global health threat, with an estimated 100,000 cases of CRS occurring annually worldwide, predominantly in regions with suboptimal vaccination coverage. This comprehensive review delves into the intricate details of rubella virus, encompassing its epidemiological patterns, modes of transmission, and the complex pathogenic mechanisms underlying congenital rubella syndrome

Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink.

Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy.

Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6.

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.

Determinants of influenza non-vaccination among Canadian children: insights from a nationwide survey.

To identify determinants influencing Canadian parents' decision not to vaccinate their children aged 6 months to 17 years against seasonal influenza. Data from the 2022 Childhood COVID-19 Immunization Coverage Survey, a national survey of approximately 10,500 Canadian parents/guardians and their children, was analyzed. The survey examined influenza vaccine coverage, parental perspectives on vaccines, reasons for hesitancy, and factors influencing immunization. Socio-demographic characteristics, including ethnicity, household income, working sector, educational attainment, and prevalence of chronic medical conditions among children were considered. Historical vaccine uptake and the impact of the COVID-19 pandemic on immunization decisions were also reviewed. Key determinants of non-vaccination in the 2021-2022 influenza season were analyzed using multivariable logistic regression, with a statistical significance level set at p-value <0·05. 70% of children aged 6 months to 17 years did not receive the seasonal influenza vaccine. Key predictors for non-vaccination included: residing in rural settings (aOR 1·35, 95% CI 1·13-1·60), parental education attainment of less than high school (aOR 2·48, 95% CI 1·24-4·97), and the absence of chronic medical conditions in children (aOR 1.60, 95% CI 1.34-1.91)· Other strong predictors included lower household income; deterrence due to the COVID-19 pandemic; and parental hesitancy stemming from concerns about the vaccine's safety, effectiveness, and by beliefs that their child was not at risk of contracting the influenza or severe consequences from the infection. This research underscores pivotal determinants of parental decisions not to vaccinate their children against seasonal influenza and sheds light on the impact of the COVID-19 pandemic. The results highlight the importance of addressing safety concerns and providing clear information to alleviate hesitancy.

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology

BackgroundDupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. ObjectiveTo perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. MethodsA systematic review of the literature was performed, and an expert Delphi Panel was assembled. ResultsThe available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. ConclusionVaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Efficacy, reactogenicity, and safety of the adjuvanted recombinant zoster vaccine for the prevention of herpes zoster in Chinese adults ≥ 50 years: A randomized, placebo-controlled trial

ABSTRACT Phase III multi-country studies (ZOE-50/70) demonstrated that the adjuvanted recombinant zoster vaccine (RZV) was well tolerated and prevented herpes zoster (HZ) in healthy ≥ 50-year-olds, with a vaccine efficacy (VE) > 90% across age groups. These pivotal trials did not enroll participants from mainland China where RZV is licensed, therefore similar clinical data are missing for this population. In this phase IV observer-blind study (NCT04869982) conducted between 2021 and 2023 in China, immunocompetent and medically stable ≥ 50-year-olds were randomized 1:1 to receive two RZV or placebo doses, 2 months apart. This study assessed the VE (overall, as confirmatory objective, and descriptively by age category [50–69-year-olds/≥ 70-year-olds]), reactogenicity, and safety of RZV in this Chinese population. Of the 6138 enrolled participants, 99.2% completed the study. During a mean follow-up period of 15.2 (±1.1) months, 31 HZ episodes were confirmed (RZV = 0; placebo = 31) for an incidence rate of 0.0 vs 8.2 per 1000 person-years and an overall VE of 100% (89.82–100). The descriptive VE was 100% (85.29–100) for 50–69-year-olds and 100% (60.90–100) for ≥ 70-year-olds. Solicited adverse events (AEs) were more frequent in the RZV vs the placebo group (median duration: 1–3 days for both groups). Pain and fatigue were the most frequent local and general AEs (RZV: 72.1% and 43.4%; placebo: 9.2% and 5.3%). The frequencies of unsolicited AEs, serious AEs, potential immune-mediated diseases, and deaths were similar between both groups. RZV is well tolerated and efficacious in preventing HZ in Chinese ≥ 50-year-olds, consistent with efficacy studies including worldwide populations with similar age and medical characteristics.

Parents’ attitudes towards the No Jab No Play legislation in Western Australia: a mixed methods study

BackgroundMandates provide a relatively cost-effective strategy to increase vaccinate rates. Since 2014, five Australian states have implemented No Jab No Play (NJPlay) policies that require children to be fully immunised to attend early childhood education and childcare services. In Western Australia, where this study was conducted, NJNPlay legislation was enacted in 2019. While most Australian families support vaccine mandates, there are a range of complexities and unintended consequences for some families. This research explores the impact on families of the NJNPlay legislation in Western Australia (WA).MethodsThis mixed-methods study used an online parent/carer survey (n = 261) representing 427 children and in-depth interviews (n = 18) to investigate: (1) the influence of the NJNPlay legislation on decision to vaccinate; and (2) the financial and emotional impacts of NJNPlay legislation. Descriptive and bivariate tests were used to analyse the survey data and open-ended questions and interviews were analysed using reflexive thematic analysis to capture the experience and the reality of participants.ResultsApproximately 60% of parents intended to vaccinate their child. Parents who had decided not to vaccinate their child/ren were significantly more likely to experience financial [p < 0.001] and emotional impacts [p < 0.001], compared to those who chose to vaccinate because of the mandate. Qualitative data were divided with around half of participants supporting childhood immunisation and NJNPlay with others discussing concerns. The themes (a) belief in the importance of vaccination and ease of access, (b) individual and community protection, and (c) vaccine effectiveness, safety and alternatives help understand how parents’ beliefs and access may influence vaccination uptake. Unintended impacts of NJNPlay included: (a) lack of choice, pressure and coercion to vaccinate; (b) policy and community level stigma and discrimination; (c) financial and career impacts; and (d) loss of education opportunities.ConclusionsParents appreciation of funded immunisation programs and mandates which enhance individual and community protection was evident. However for others unintended consequences of the mandate resulted in significant social, emotional, financial and educational impacts. Long-term evidence highlights the positive impact of immunisation programs. Opinions of impacted families should be considered to alleviate mental health stressors.

Coronavirus disease 2019 vaccination in patients with rheumatic diseases: A bibliometric‐based analysis of trends

AbstractBackgroundCoronavirus disease 2019 (COVID‐19) vaccination in patients with rheumatic disease is of practical clinical importance. This study aimed to perform a comprehensive bibliometric analysis of COVID‐19 vaccination in patients with rheumatic disease and indicate possible directions for future studies.MethodsResearch articles and reviews related to COVID‐19 vaccinations in patients with rheumatic diseases were retrieved from Science Citation Index Expanded of the Web of Science Core Collection. The CiteSpace and VOSviewer software were used to depict network mapping showing the collaborations among countries, institutions, and authors. Current hotspots and future directions were derived by analyzing highly cited/co‐cited documents and keywords.ResultsIn total, 615 documents published in 194 academic journals, including 505 articles and 110 reviews contributed by 5068 authors from 1693 institutions in 79 countries/regions, were finally included and analyzed. The United States and the University of London were the most productive country and cooperative institution, respectively. Author analysis showed that cooperation between different authors was largely confined to only several groups. Vaccines and Journal of the American Academy of Dermatology were the journals with the most publications and citations per document, respectively. Cluster analysis showed that the keywords can be categorized into groups like kidney disease, antibody response, COVID‐19 vaccine, vaccination, validation, safety, and giant cell arteritis.ConclusionsThe efficacy and safety of COVID‐19 vaccination in patients with rheumatic disease are being continuously investigated. Future studies on COVID‐19 vaccination in patients with rheumatic diseases could focus on antibody response, validation, and vaccine safety.

COVID-19 Vaccine Effectiveness and Digital Pandemic Surveillance in Germany (eCOV Study): Web Application-Based Prospective Observational Cohort Study.

The COVID-19 pandemic posed significant challenges to global health systems. Efficient public health responses required a rapid and secure collection of health data to improve the understanding of SARS-CoV-2 and examine the vaccine effectiveness (VE) and drug safety of the novel COVID-19 vaccines. This study (COVID-19 study on vaccinated and unvaccinated subjects over 16 years; eCOV study) aims to (1) evaluate the real-world effectiveness of COVID-19 vaccines through a digital participatory surveillance tool and (2) assess the potential of self-reported data for monitoring key parameters of the COVID-19 pandemic in Germany. Using a digital study web application, we collected self-reported data between May 1, 2021, and August 1, 2022, to assess VE, test positivity rates, COVID-19 incidence rates, and adverse events after COVID-19 vaccination. Our primary outcome measure was the VE of SARS-CoV-2 vaccines against laboratory-confirmed SARS-CoV-2 infection. The secondary outcome measures included VE against hospitalization and across different SARS-CoV-2 variants, adverse events after vaccination, and symptoms during infection. Logistic regression models adjusted for confounders were used to estimate VE 4 to 48 weeks after the primary vaccination series and after third-dose vaccination. Unvaccinated participants were compared with age- and gender-matched participants who had received 2 doses of BNT162b2 (Pfizer-BioNTech) and those who had received 3 doses of BNT162b2 and were not infected before the last vaccination. To assess the potential of self-reported digital data, the data were compared with official data from public health authorities. We enrolled 10,077 participants (aged ≥16 y) who contributed 44,786 tests and 5530 symptoms. In this young, primarily female, and digital-literate cohort, VE against infections of any severity waned from 91.2% (95% CI 70.4%-97.4%) at week 4 to 37.2% (95% CI 23.5%-48.5%) at week 48 after the second dose of BNT162b2. A third dose of BNT162b2 increased VE to 67.6% (95% CI 50.3%-78.8%) after 4 weeks. The low number of reported hospitalizations limited our ability to calculate VE against hospitalization. Adverse events after vaccination were consistent with previously published research. Seven-day incidences and test positivity rates reflected the course of the pandemic in Germany when compared with official numbers from the national infectious disease surveillance system. Our data indicate that COVID-19 vaccinations are safe and effective, and third-dose vaccinations partially restore protection against SARS-CoV-2 infection. The study showcased the successful use of a digital study web application for COVID-19 surveillance and continuous monitoring of VE in Germany, highlighting its potential to accelerate public health decision-making. Addressing biases in digital data collection is vital to ensure the accuracy and reliability of digital solutions as public health tools.