UNASSIGNED: The World Health Organization recently revised their recommendations and considered healthy children and adolescents as low priority group for COVID-19 vaccine. This review comprehensively assessed existing clinical evidence on COVID-19 vaccine in 12-17 years old.
UNASSIGNED: Included in this review were any type of study that investigated the efficacy, immunogenicity, safety, and effectiveness of COVID-19 vaccine on protection against SARS-COV-2 infection in 12-17 years old. Various electronic databases were searched up to March 15, 2023. Studies were screened, data extracted, risk of bias appraised, and certainty of evidence was judged using GRADE. Review Manager 5.4 was used to estimate pooled effects. Difference between the two groups was described as mean difference for continuous variables and as relative risk or odds ratio for categorical variables.
UNASSIGNED: There were six randomized controlled trials and 16 effectiveness studies (8 cohorts and 8 case control). Low certainty evidence showed that BNT162b2 (Pfizer) was effective, immunogenic, and safe in healthy adolescents. There were 15 effectiveness studies on BNT162b2 (Pfizer) in healthy adolescent and one on immunocompromised patients. It was protective against infection with any of the variants, with higher protection against Delta than Omicron. BNT162b2 is protective against hospitalization and emergency and urgent care (high certainty); and critical care and MIS-C (low). Very low certainty evidence noted that BNT 162b2 was also immunogenic in 12-21 years old with rheumatic diseases while on immunomodulatory treatment but with possible increased exacerbation of illness. Low certainty evidence demonstrated that mRNA-1273 (Moderna) was effective, immunogenic, and safe. Low to very low certainty evidence were noted on the safety and immunogenicity of two vector base vaccines (ChAdOx1-19 and Ad5 vector COVID vaccine) and two inactivated vaccines (CoronaVac and BBIBP CorV).
CONCLUSIONS: There is presently low certainty evidence on the use of RNA vaccines in 12-17 years old. The recommendation on its use is weak. There is presently insufficient evidence for the use of inactivated and vector-based COVID-19 vaccines. Different countries should consider whether to vaccinate healthy adolescent without comprising the other recommended immunization and health priorities that are crucial for this age group. Other factors including cost-effectiveness of vaccination and disease burden should be accounted.

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.

BACKGROUND: Patients with autoimmune and immune-mediated diseases (AI-IMD) are at greater risk of COVID-19 infection; therefore, they should be prioritized in vaccination programs. However, there are concerns regarding the safety of COVID-19 vaccines in terms of disease relapse, flare, or exacerbation. In this study, we aimed to provide a more precise and reliable vision using systematic review and meta-analysis.
METHODS: PubMed-MEDLINE, Embase, and Web of Science were searched for original articles reporting the relapse/flare in adult patients with AI-IMD between June 1, 2020 and September 25, 2022. Subgroup analysis and sensitivity analysis were conducted to investigate the sources of heterogeneity. Statistical analysis was performed using R software.
RESULTS: A total of 134 observations of various AI-IMDs across 74 studies assessed the rate of relapse, flare, or exacerbation in AI-IMD patients. Accordingly, the crude overall prevalence of relapse, flare, or exacerbation was 6.28% (95% CI [4.78%; 7.95%], I2 = 97.6%), changing from 6.28% (I2 = 97.6%) to 6.24% (I2 = 65.1%) after removing the outliers. AI-IMD patients administering mRNA, vector-based, and inactive vaccines showed 8.13% ([5.6%; 11.03%], I2 = 98.1%), 0.32% ([0.0%; 4.03%], I2 = 93.5%), and 3.07% ([1.09%; 5.9%], I2 = 96.2%) relapse, flare, or exacerbation, respectively (p-value = 0.0086). In terms of disease category, nephrologic (26.66%) and hematologic (14.12%) disorders had the highest and dermatologic (4.81%) and neurologic (2.62%) disorders exhibited to have the lowest crude prevalence of relapse, flare, or exacerbation (p-value < 0.0001).
CONCLUSIONS: The risk of flare/relapse/exacerbation in AI-IMD patients is found to be minimal, especially with vector-based vaccines. Vaccination against COVID-19 is recommended in this population.

The outbreak of COVID-19 started in December 2019 and spread rapidly all over the world. It became clear that the development of an effective vaccine was the only way to stop the pandemic. It was the first time in the history of infectious diseases that the process of the development of a new vaccine was conducted on such a large scale and accelerated so rapidly. At the end of 2020, the first COVID-19 vaccines were approved for marketing. At the end of March 2023, over three years after the outbreak of the COVID-19 pandemic, 199 vaccines were in pre-clinical development and 183 in clinical development. The candidate vaccines in the clinical phase are based on the following platforms: protein subunit, DNA, RNA, non-replication viral vector, replicating viral vector, inactivated virus, virus-like particles, live attenuated virus, replicating viral vector combined with an antigen-presenting cell, non-replication viral vector combined with an antigen-presenting cell, and bacterial antigen-spore expression vector. Some of the new vaccine platforms have been approved for the first time for human application. This review presents COVID-19 vaccines currently available in the world, procedures for assurance of the quality and safety of the vaccines, the vaccinated population, as well as future perspectives for the new vaccine platforms in drug and therapy development for infectious and non-infectious diseases.

Cerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the so-called venous stroke. Current guidelines recommend anticoagulants as first-line therapy in the treatment of venous stroke. With complicated causes of cerebral venous thrombosis, treatment is difficult, especially when combined with autoimmune diseases, blood diseases, and even COVID-19.
This review summarizes the pathophysiological mechanisms, epidemiology, diagnosis, treatment, and clinical prognosis of cerebral venous thrombosis combined with autoimmune diseases, blood diseases, or infectious diseases such as COVID-19.
A systematic understanding of particular risk factors that should not be neglected when unconventional cerebral venous thrombosis occurs and for a scientific understanding of pathophysiological mechanisms, clinical diagnosis, and treatment, thus contributing to knowledge on special types of venous stroke.

Streptococcus suis (S. suis) is a bacterial pathogen of pigs that has a major animal health and economic impact on the pig industry. Bovine herpesvirus-4 (BoHV-4) is a new virus-based vaccine vector that has been used for the immunogenic delivery of antigens from a variety of pathogens. In the present study, two recombinant BoHV-4-based vectors were evaluated for their ability to induce immunity and protection against S. suis in a rabbit model. The GMD protein is a fusion protein consisting of multiple dominant B-cell epitopes ((B-cell dominant epitopes of GAPDH, MRP, and DLDH antigens) (BoHV-4/GMD)) and the second suilysin (SLY) (BoHV-4/SLY) from S. suis serotype 2 (SS2). Both GMD and SLY delivered by the BoHV-4 vectors were recognized by sera from SS2-infected rabbits. The vaccination of rabbits with the BoHV-4 vectors induced antibodies against SS2, as well as against additional S. suis serotypes, SS7 and SS9. However, sera from BoHV-4/GMD-vaccinated animals promoted a significant level of phagocytic activity by pulmonary alveolar macrophages (PAMs) against SS2, SS7, and SS9. In contrast, sera from rabbits immunized with BoHV-4/SLY induced PAM phagocytic activity against only SS2. In addition, BoHV-4 vaccines differed in the associated level of protection against lethal SS2 challenge, which ranged from high (71.4%) to low (12.5%) for BoHV-4/GMD and BoHV-4/SLY, respectively. These data suggest BoHV-4/GMD as a promising vaccine candidate against S. suis disease.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination.
METHODS:  We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS-CVST versus non-TTS-CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS-CVST compared to non-TTS-CVST; and (4) the dependency or death at discharge among TTS-CVST compared to non-TTS-CVST cases.
RESULTS: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS-CVST (OR: 52.34, 95% CI 9.58-285.98). TTS-CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96-44.60) and death or dependency at discharge compared to non-TTS-CVST (OR: 6.70; 95% CI 3.15-14.26). TTS-CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI - 12.64 to - 0.45], affecting younger patients (MD:-9.00 years; 95% CI - 14.02 to - 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26-4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31-9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51-39.98) compared to non-TTS-CVST cases.
CONCLUSIONS: TTS-CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS-CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS-CVST cases following COVID-19 vaccination.

The hepatitis E virus (HEV) is a major global health problem, leading to large outbreaks in the developing world and chronic infections in the developed world. HEV is a non-enveloped virus, which circulates in the blood in a quasi-enveloped form. The quasi-envelope protects HEV particles from neutralising anti-capsid antibodies in the serum; however, most vaccine approaches are designed to induce an immune response against the HEV capsid. In this study, we explored systemic in vivo administration of a novel synthetic and myotropic Adeno-associated virus vector (AAVMYO3) to express the small HEV phosphoprotein ORF3 (found on quasi-enveloped HEV) in the musculature of mice, resulting in the robust and dose-dependent formation of anti-ORF3 antibodies. Neutralisation assays using the serum of ORF3 AAV-transduced mice showed a modest inhibitory effect on the infection of quasi-enveloped HEV in vivo, comparable to previously characterised anti-ORF3 antibodies used as a control. The novel AAVMYO3 capsid used in this study can serve as a versatile platform for the continued development of vector-based vaccines against HEV and other infectious agents, which could complement traditional vaccines akin to the current positive experience with SARS-CoV-2.

OBJECTIVE: The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or RNA in respiratory specimens ≥14 days after administration of all recommended doses of authorized coronavirus disease 2019 (COVID-19) vaccines is defined as breakthrough infection. In the present investigation, mRNA and vector-based SARS-CoV-2 vaccines were analysed with respect to postvaccination infections in vaccinated hospital employees.
METHODS: A total of 8553 staff members were vaccinated with BNT162b2 (47%) or ChAdOx1-S (53%) between January and May 2021. In a retrospective observational cohort study, incidence of SARS-CoV-2 postvaccination infections was analysed in relation to demographic data, viral load, virus variants, vaccine brand and vaccination status at time of positive PCR test (fully vaccinated: ≥14 days since second dose; partially vaccinated: >21 days since first, but <14 days after second dose; insufficiently vaccinated: <22 days since first dose).
RESULTS: Within the follow-up period, ending on 31 July 2021, person-time at risk-adjusted monthly rates for SARS-CoV-2 postvaccination infections were 0.18% (BNT162b2) and 0.57% (ChAdOx1-S) for insufficiently vaccinated, 0.34% (BNT162b2) and 0.32% (ChAdOx1-S) for partially vaccinated and 0.06% (BNT162b2) and 0.04% (ChAdOx1-S) for fully vaccinated participants. The two vaccine types did not differ with respect to hazard ratios for any of the respective postvaccination infection types. No cases of COVID-19-related hospitalizations or deaths were reported. Genotyping of positive PCR specimens revealed 42 variants of concern: B.1.1.7 (Alpha variant; n = 34); B.1.351 (Beta variant; n = 2), B.1.617.2 (Delta variant; n = 6).
CONCLUSIONS: BNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered.

From December 2014 to June 2015, a novel H5 Eurasian A/goose/Guangdong (Gs/GD) lineage clade 2.3.4.4 high pathogenicity avian influenza (HPAI) virus caused the largest animal health emergency in US history resulting in mortality or culling of greater than 48 million poultry. The outbreak renewed interest in developing intervention strategies, including vaccines, for these newly emergent HPAI viruses. In these studies, several existing H5 vaccines or vaccine seed strains with varying genetic relatedness (85-100%) to the 2.3.4.4 HPAI viruses were evaluated for protection in poultry. Chickens received a single dose of either an inactivated whole H5 AI vaccine, or a recombinant fowl poxvirus or turkey herpesvirus-vectored vaccines with H5 AI hemagglutinin gene inserts followed by challenge with either a U.S. wild bird H5N8 (A/gyrfalcon/Washington/40188-6/2014) or H5N2 (A/northern pintail/Washington/40964/2014) clade 2.3.4.4 isolate. Results indicate that most inactivated H5 vaccines provided 100% protection from lethal effects of H5N8 or H5N2 challenge. In contrast, the recombinant live vectored vaccines only provided partial protection which ranged from 40 to 70%. Inactivated vaccine groups, in general, had lower number of birds shedding virus and at lower virus titers then the recombinant vaccine groups. Interestingly, prechallenge antibody titers using the HPAI challenge viruses as antigen in heterologous vaccine groups were typically low (≤2 log2), yet the majority of these birds survived challenge. Taken together, these studies suggest that existing vaccines when used in a single immunization strategy may not provide adequate protection in poultry against the 2.3.4.4 HPAI viruses. Updating the H5 hemagglutinin to be genetically closer to the outbreak virus and/or using a prime-boost strategy may be necessary for optimal protection.