Neutralizing-antibody-independent SARS-CoV-2 control correlated with intranasal-vaccine-induced CD8+ T cell responses

Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-...

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Published in:Cell reports. Medicine 2022-02, Vol.3 (2), p.100520-100520, Article 100520
Main Authors: Ishii, Hiroshi, Nomura, Takushi, Yamamoto, Hiroyuki, Nishizawa, Masako, Thu Hau, Trang Thi, Harada, Shigeyoshi, Seki, Sayuri, Nakamura-Hoshi, Midori, Okazaki, Midori, Daigen, Sachie, Kawana-Tachikawa, Ai, Nagata, Noriyo, Iwata-Yoshikawa, Naoko, Shiwa, Nozomi, Suzuki, Tadaki, Park, Eun-Sil, Ken, Maeda, Onodera, Taishi, Takahashi, Yoshimasa, Kusano, Kohji, Shimazaki, Ryutaro, Suzaki, Yuriko, Ami, Yasushi, Matano, Tetsuro
Format: Article
Language:English
Subjects:
Administration, Intranasal - methods
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
CD8+ T cell
CD8-Positive T-Lymphocytes - immunology
Chlorocebus aethiops
Coronavirus Envelope Proteins - immunology
Coronavirus M Proteins - immunology
Coronavirus Nucleocapsid Proteins - immunology
COVID-19
COVID-19 - epidemiology
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 - virology
COVID-19 Vaccines - administration & dosage
COVID-19 Vaccines - immunology
Disease Models, Animal
Female
intranasal
Macaca fascicularis
Male
Pandemics - prevention & control
Phosphoproteins - immunology
SARS-CoV-2 - immunology
Spike Glycoprotein, Coronavirus - immunology
Treatment Outcome
Vaccination - methods
vaccine
variant
Vero Cells
Viral Load
viral vector
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Summary:Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants. Here, we investigate the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Seven vaccinated macaques exhibit significantly reduced viral load in nasopharyngeal swabs on day 2 post-challenge compared with nine unvaccinated controls. The viral control in the absence of SARS-CoV-2-specific NAbs is significantly correlated with vaccine-induced, viral-antigen-specific CD8+ T cell responses. Our results indicate that CD8+ T cell induction by intranasal vaccination can result in NAb-independent control of SARS-CoV-2 infection, highlighting a potential of vaccine-induced CD8+ T cell responses to contribute to COVID-19 containment. [Display omitted] •Anti-SARS-CoV-2 efficacy of an intranasal S-free vaccine is shown in macaques•The SARS-CoV-2 control is associated with vaccine-induced CD8+ T cell responses•Vaccine induction of CD8+ T cells can result in neutralization-free viral control•Vaccine-induced CD8+ T cells may contribute to SARS-CoV-2 variant control Ishii et al. show neutralization-independent SARS-CoV-2 control associated with vaccine-induced CD8+ T cell responses, indicating that virus-specific CD8+ T cell induction by intranasal vaccination can result in SARS-CoV-2 control. Results highlight the potential of vaccine-induced CD8+ T cell responses to contribute to the control of SARS-CoV-2 variants.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2022.100520