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Immunization via the respiratory route is predicted to increase the effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate the immunogenicity and protective efficacy of one or two doses of a live-attenuated murine pneumonia virus vector expressing SARS-CoV-2 prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally to male rhesus macaques. A single dose of MPV/S-2P is highly immunogenic, and a second dose increases the magnitude and breadth of the mucosal and systemic anti-S antibody responses and increases levels of dimeric anti-S IgA in the airways. MPV/S-2P also induces S-specific CD4 + and CD8 + T-cells in the airways that differentiate into large populations of tissue-resident memory cells within a month after the boost. One dose induces substantial protection against SARS-CoV-2 challenge, and two doses of MPV/S-2P are fully protective against SARS-CoV-2 challenge virus replication in the airways. A prime/boost immunization with a mucosally-administered live-attenuated MPV vector could thus be highly effective in preventing SARS-CoV-2 infection and replication., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4 + and CD8 + T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine., Competing Interests: Declaration of interests X.L., C.L., C.L.N., S.M., and U.J.B. are inventors on the provisional patent application number 63/180,534, entitled “recombinant chimeric B/HPIV3 expressing SARS-CoV-2 spike protein and its use,” filed by the United States Department of Health and Human Services., (Published by Elsevier Inc.)

This review is designed to assist both individuals and organizations involved in animal-based research to understand and appreciate the importance and potential risks of compassion fatigue and euthanasia stress. We reviewed current literature regarding compassion fatigue and euthanasia stress as they relate to the laboratory animal science community. Definitions, recognition, and mitigation steps are clarified. We offer educational and mitigation advice and present needs for future research on these topics that is related directly to the laboratory animal science community.

Mucosal-associated invariant T cells (MAITs) are positioned in airways and may be important in the pulmonary cellular immune response against Mycobacterium tuberculosis infection, particularly prior to priming of peptide-specific T cells. Accordingly, there is interest in the possibility that boosting MAITs through tuberculosis (TB) vaccination may enhance protection, but MAIT responses in the lungs during tuberculosis are poorly understood. In this study, we compared pulmonary MAIT and peptide-specific CD4 T cell responses in M. tuberculosis -infected rhesus macaques using 5-OP-RU-loaded MR-1 tetramers and intracellular cytokine staining of CD4 T cells following restimulation with an M. tuberculosis -derived epitope megapool (MTB300), respectively. Two of four animals showed a detectable increase in the number of MAIT cells in airways at later time points following infection, but by ∼3 weeks postexposure, MTB300-specific CD4 T cells arrived in the airways and greatly outnumbered MAITs thereafter. In granulomas, MTB300-specific CD4 T cells were ∼20-fold more abundant than MAITs. CD69 expression on MAITs correlated with tissue residency rather than bacterial loads, and the few MAITs found in granulomas poorly expressed granzyme B and Ki67. Thus, MAIT accumulation in the airways is variable and late, and MAITs display little evidence of activation in granulomas during tuberculosis in rhesus macaques., (Copyright © 2018 American Society for Microbiology.)