期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.995235
关键词
SARS-CoV-2; vaccine candidates; MVA; S protein; intranasal delivery; immunogenicity; protective efficacy; mice
类别
资金
- Fondo COVID-19 grant
- [Instituto de Salud Carlos III (ISCIII)], Fondo Supera COVID-19 grant
- Spanish Research Council (CSIC)
- CSIC
- la Caixa Banking Foundation
- MAPFRE donations
- Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency (AEI)
- European Commission-NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global)
- Spanish State Research Agency
- MCIN
- ISCIII
- European Commission
- Fundacioin Caixa-Health Research
- [COV20/00151]
- [202120E079]
- [CF01-00008]
- [PID2020-114481RB-I00]
- [HR18-00469]
- [2020E84]
- [10.13039/501100011033]
Intranasal administration of vaccines can induce mucosal and systemic immune responses, protecting animals from SARS-CoV-2 infection and preventing virus transmission.
Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4(+) and cytotoxic CD8(+) T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.
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