Localized and Systemic Immune Responses against SARS-CoV-2 Following Mucosal Immunization.

Shaswath S Chandrasekar,Yashdeep Phanse,Rachel E Hildebrand,Jorge E Osorio,Mostafa Hanafy,Chungyi H Hansen,Chia-Wei Wu,Adel M Talaat,M Suresh

doi:10.3390/vaccines9020132

Abstract

The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when used against avian coronavirus. Here, we report on the immune responses elicited by mucosal homologous plasmid and a heterologous immunization strategy using a plasmid vaccine and a Modified Vaccinia Ankara (MVA) expressing SARS-CoV-2 spike (S) and nucleocapsid (N) antigens. Only the heterologous intranasal immunization strategy elicited neutralizing antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice, suggesting a protective vaccine. The same prime/boost strategy led to the induction of type 1 and type 17 T-cell responses and polyfunctional T-cells expressing multiple type 1 cytokines (e.g., IFN-γ, TNFα, IL-2) in the lungs and spleens of vaccinated mice. In contrast, the plasmid homologous vaccine strategy led to the induction of local mono and polyfunctional T-cells secreting IFN-γ. Outcomes of this study support the potential of QAC-nano vaccines to elicit significant mucosal immune responses against respiratory coronaviruses.

Highlights

COVID-19 represents a significant challenge to public health authorities worldwide because of the speed of disease transmission and the lack of effective treatment or prevention strategies [1]
The work presented here profiles the type of immune responses elicited by different mucosal vaccination strategies
We theorize that the heterologous vaccine strategy might be better at providing sterilizing immunity against SARS-CoV-2

Summary

Introduction

COVID-19 represents a significant challenge to public health authorities worldwide because of the speed of disease transmission and the lack of effective treatment or prevention strategies [1]. Live-attenuated vaccines have been shown to induce an antibodydependent enhancement effect worsening the clinical outcome of rhesus macaques infected with SARS-CoV [3]. Other vaccination strategies such as subunit, RNA-based, and viral vector vaccines have advantages over traditional vaccines; their use faces many challenges. There is a need for rapid development of vaccines. For viral vectored vaccines like the Modified Vaccinia Ankara (MVA) strain, highly efficient scale-up production processes have been set-up already, enabling its utility during a pandemic such as COVID-19 [6]

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Discussion

Conclusion