tetano
Editor, Senior Moderator
Front Immunol
. 2022 Sep 12;13:995235.
doi: 10.3389/fimmu.2022.995235. eCollection 2022.
Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection
Patricia Pérez[SUP] 1 2 [/SUP], David Astorgano[SUP] 1 [/SUP], Guillermo Albericio[SUP] 1 [/SUP], Sara Flores[SUP] 1 [/SUP], Pedro J Sánchez-Cordón[SUP] 3 [/SUP], Joanna Luczkowiak[SUP] 2 4 [/SUP], Rafael Delgado[SUP] 2 4 5 [/SUP], José M Casasnovas[SUP] 6 [/SUP], Mariano Esteban[SUP] 1 [/SUP], Juan García-Arriaza[SUP] 1 2 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] and cytotoxic CD8[SUP]+[/SUP] 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.
Keywords: MVA; S protein; SARS-CoV-2; immunogenicity; intranasal delivery; mice; protective efficacy; vaccine candidates.
. 2022 Sep 12;13:995235.
doi: 10.3389/fimmu.2022.995235. eCollection 2022.
Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection
Patricia Pérez[SUP] 1 2 [/SUP], David Astorgano[SUP] 1 [/SUP], Guillermo Albericio[SUP] 1 [/SUP], Sara Flores[SUP] 1 [/SUP], Pedro J Sánchez-Cordón[SUP] 3 [/SUP], Joanna Luczkowiak[SUP] 2 4 [/SUP], Rafael Delgado[SUP] 2 4 5 [/SUP], José M Casasnovas[SUP] 6 [/SUP], Mariano Esteban[SUP] 1 [/SUP], Juan García-Arriaza[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36172368
- PMCID: PMC9510595
- DOI: 10.3389/fimmu.2022.995235
Abstract
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[SUP]+[/SUP] and cytotoxic CD8[SUP]+[/SUP] 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.
Keywords: MVA; S protein; SARS-CoV-2; immunogenicity; intranasal delivery; mice; protective efficacy; vaccine candidates.