ABSTRACT
From the approval of the first COVID-19 vaccine in December 2020 up to 2 October 2022, 68% of the world population received at least one dose of COVID-19 vaccine and more than 12 billion doses have been administered globally.1 In the meantime, the pandemic became more complex due to the new circulating COVID-19 virus variants. The emergence of the alpha, beta, delta and omicron SARS-CoV-2 variants were associated with new waves of infections. Even so, several studies showed that vaccination using the COVID-19 vaccines formulated against the nonmutated spike protein have remained effective in preventing severe COVID-19, hospitalization, and death. The safety surveillance of the COVID- 19 vaccine represented a challenge given the unprecedented scenario present in this pandemic. Challenges and factors to consider include the following: 1. Administration to many individuals in a short time;2. Staggered distribution prioritizing individuals at highest risk;3. High number of reported AEs in an environment of hyper-pharmacovigilance;4. Product availability;5. Regional public health recommendations that differed from clinical trial scenarios;and 6. New mutations in the circulating virus. All these aspects need to be considered for a proper evaluation of the safety profile of each COVID-19 vaccine. The Pfizer/BioNTech booster dose (3 and 4) has a favourable safety and benefit-risk profile. The safety profile after administration of booster doses was similar to that seen for the primary doses where the elderly and medically frail subjects with multiple comorbidities reported different adverse events than other populations, such as young or healthy people vaccinated at a later time point. With a broader population (including healthy individuals, adults, adolescent, children and infants) now boosted, the safety profile appears stable and confirms a favourable benefit-risk profile. Overall, the most commonly reported adverse events were local and systemic known reactogenicity events, consistent with clinical trial data, and events related to the pandemic situation (inappropriate schedule of product administration and heterologous vaccinations). The pandemic is not over yet, and now countries have begun to authorize the bivalent COVID-19 vaccines covering previous and newer variants of concern.
ABSTRACT
Background. Respiratory syncytial virus (RSV) is an important cause of disease in older adults and is associated with high morbidity and mortality, especially in those with high-risk conditions. Illness can vary from mild upper respiratory tract symptoms to more severe lower respiratory tract disease. After over 50 years of research, there is now hope for an RSV vaccine for any population, including older adults. An investigational bivalent RSV A and B, stabilized RSV prefusion F subunit vaccine (RSVpreF) was assessed successfully in a pivotal phase 3 efficacy study in older adults. (NCT05035212). Methods. The primary efficacy objective of this Phase 3, global, multicenter, randomized, double-blinded, placebo-controlled study was to evaluate the prevention of RSV associated lower respiratory tract illness (LRTI-RSV) in up to 40,000 adults >=60 years of age during the first winter season (September 2021-June 2022). Two primary endpoints were tested sequentially - LRTI-RSV with >=2 and >=3 symptoms. A pre-planned efficacy interim analysis (IA) was to be conducted by an external Data Monitoring Committee (DMC) upon accrual of at least 29 cases of LRTI-RSV with >=2 symptoms. With efficacy demonstrated for cases with >=2 symptoms and sufficient cases with >= 3 symptoms accrued, an efficacy analysis of cases with >= 3 symptoms was to be conducted. The ongoing study is collecting additional safety and descriptive efficacy data. Results. At the time of the IA, approximately 34,000 participants received either RSVpreF 120 mug (60 mug each of RSVpreF from RSV A and RSV B) or placebo (1:1 randomization). Forty-four LRTI-RSV cases with >=2 symptoms were accrued with 11 cases in the RSVpreF group and 33 cases in the placebo group corresponding to a VE of 66.7% (96.66% CI: 28.8%, 85.8%). Sixteen LRTI-RSV cases with >=3 symptoms were accrued with 2 cases in the RSVpreF group and 14 cases in the placebo group corresponding to a VE of 85.7% (96.66% CI: 32.0%, 98.7%). The investigational vaccine was well-tolerated with no safety concerns. Conclusion. Despite unpredictable RSV activity due to the COVID-19 pandemic, the primary objective of the study was met demonstrating that RSVpreF had a favorable safety profile and was highly efficacious in preventing LRTI-RSV with >=2 symptoms and >=3 symptoms in older adults 60 years and older.