Vaccination in children with immune-mediated disorders.

OBJECTIVE: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. SOURCE OF DATA: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. DATA SYNTHESIS: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immune-mediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. CONCLUSIONS: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

Propagation of SARS-CoV-2 in a Closed Cell Culture Device: Potential GMP Compatible Production Platform for Live-Attenuated Vaccine Candidates under BSL-3 Conditions?

Live-attenuated SARS-CoV-2 vaccines present themselves as a promising approach for the induction of broad mucosal immunity. However, for initial safety assessment in clinical trials, virus production requires conditions meeting Good Manufacturing Practice (GMP) standards while maintaining biosafety level 3 (BSL-3) requirements. Since facilities providing the necessary complex ventilation systems to meet both requirements are rare, we here describe a possibility to reproducibly propagate SARS-CoV-2 in the automated, closed cell culture device CliniMACS Prodigy® in a common BSL-3 laboratory. In this proof-of-concept study, we observed an approximately 300-fold amplification of SARS-CoV-2 under serum-free conditions with high lot-to-lot consistency in the infectious titers obtained. With the possibility to increase production capacity to up to 3000 doses per run, this study outlines a potential fast-track approach for the production of live-attenuated vaccine candidates based on highly pathogenic viruses under GMP-like conditions that may contribute to pandemic preparedness.

Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines.

Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013-2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues.

Effectiveness of Booster Measles-Mumps-Rubella Vaccination in Lower COVID-19 Infection Rates: A Retrospective Cohort Study in Turkish Adults.

OBJECTIVE: The aim of this study was to investigate the effectiveness of booster vaccination of adults with measles-mumps-rubella in the COVID-19 infection rates. METHODS: In order to investigate this hypothesis, we tested COVID-19 positivity rate through PCR assay on the participants (n=245; male), who had to share the same student accommodation together with the same dining hall to provide governmental service. Participants were divided into two groups based on their booster vaccination status with measles-mumps-rubella: the non-vaccinated group (n=207) and the vaccinated group (n=38). The rate of COVID-19 seropositivity, age, body mass index (BMI), active smoking and presence of comorbidity were also measured and recorded. RESULTS: All of the participants were healthy, and age distribution, comorbidity rates, active smoking status and BMI did not vary significantly among the two groups (p=0.305, p=0.594, p=0.280, and p=0.922, respectively). About 36.7% (n=90) of the participants were found to be COVID-19 positive by PCR among which the non-vaccinated cases had higher rates of COVID-19 seropositivity than the vaccinated cases (40.6% vs 15.8%) (OR=3.6, 95%CI: 1.5-9.0, p=0.004). CONCLUSION: Based on these results, we cautiously predict that immunity produced by MMR vaccination boosters may provide some degree of protection against COVID-19 in the adult population.

Could "trained immunity" be induced by live attenuated vaccines protect against COVID-19? Review of available evidence.

Coronavirus disease 2019 (COVID-19) represents a severe global public health threat. Caused by SARS-Cov-2, COVID-19 is characterized by high transmission rate that correlates with high viral load. The full clinical spectrum of the illness, the prevalence rates of mild symptomatic and asymptomatic cases, and the case fatality rates are still poorly understood, highlighting the importance of early preventive measures. Unfortunately, appropriate vaccination against SARS-Cov-2 is not yet available. Unless a target vaccine is developed, COVID-19 impacts will be devastating. "Trained immunity" (TI), which could be induced by live attenuated vaccines (LAVs), is a potential public health preventive approach to boost the host immune system. Trained innate immune cells demonstrated phenotypical and functional changes leading them to acquire immunological memory and amplify their responses against subsequent infections. This phenomenon could have important public health preventive implications by harnessing the early immune responses against COVID-19, restricting its progression, and suppressing its infectivity. Some LAVs have induced a broad, nonspecific, protection against unrelated pathogens and decreased mortality from conditions other than the targeted infectious diseases. This review summarizes the relevant literature and 1) emphasizes the role of available LAVs as potential stimulants for TI and 2) proposes this phenomenon as a potential preventive approach against COVID-19 that needs thoughtful consideration and further investigation. Clinical trials in this field are then urgently needed in line of vaccine and treatment unavailability. This is specifically true when considering two evolving scenarios; the virus spread may not diminish with warm weather, and that it will erupt a second-hit severe outbreak next winter.

New Points of Departure for More Global Influenza Vaccine Use.

Each year, influenza causes a significant acute respiratory disease burden. In addition, influenza pandemics periodically occur. Annual vaccination is the best tool for influenza prevention, but its effectiveness can vary from year to year. The narrow specificity of conventional vaccines and the drug resistance of currently circulating viruses reduce the effectiveness of prophylaxis and treatment and require the development of new broad-spectrum preparations. Furthermore, the challenge of creating a highly effective universal influenza vaccine takes on renewed intensity in the face of the COVID-19 pandemic.

Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.