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

• Main Authors: Shaswath S. Chandrasekar, Yashdeep Phanse, Rachel E. Hildebrand, Mostafa Hanafy, Chia-Wei Wu, Chungyi H. Hansen, Jorge E. Osorio, M. Suresh, Adel M. Talaat
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Vaccines
• Subjects: SARS-CoV-2; COVID-19; intranasal vaccine; nanovaccine; heterologous vaccine
• Online Access: https://www.mdpi.com/2076-393X/9/2/132

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.