ABSTRACT
Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Humans , Vaccines, Attenuated , COVID-19/prevention & control , COVID-19 Vaccines , BNT162 Vaccine , Pandemics , MesocricetusABSTRACT
Live-attenuated measles virus (MeV) has been extraordinarily effective in preventing measles infections and their often deadly sequelae, accompanied by remarkable safety and stability since their first licensing in 1963. The advent of recombinant DNA technologies, combined with systems to generate infectious negative-strand RNA viruses on the basis of viral genomes encoded on plasmid DNA in the 1990s, paved the way to generate recombinant, vaccine strain-derived MeVs. These live-attenuated vaccine constructs can encode and express additional foreign antigens during transient virus replication following immunization. Effective humoral and cellular immune responses are induced not only against the MeV vector, but also against the foreign antigen cargo in immunized individuals, which can protect against the associated pathogen. This review aims to present an overview of the versatility of this vaccine vector as platform technology to target various diseases, as well as current research and developmental stages, with one vaccine candidate ready to enter phase III clinical trials to gain marketing authorization, MV-CHIK.
ABSTRACT
Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.