Activation of IgG antibody and mucosal T cell responses to MERS-CoV in human nasopharynx-associated lymphoid tissue by a ChAdOx1 vectored vaccine candidate and inactivated MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV) causes serious infection in humans with up to 40% mortality. As MERS-CoV infects humans via nasopharyngeal mucosa, local mucosal immunization may provide an effective vaccination strategy. Nasopharynx-associated lymphoid tissues (NALT, comprising adenotonsillar tissues) are immune induction sites for intranasal vaccines. We studied the capacity of a viral vectored MERS candidate vaccine (ChAdOx1 MERS) and inactivated MERS-CoV in activating cellular and antibody responses in the NALT. Mononuclear cells isolated from adenotonsillar tissues from children and adults were stimulated with ChAdOx1 MERS and heat- or radiation-inactivated MERS-CoV, followed by analysis of anti-MERS IgG antibody and cytokines (IFNγ and TNFα) in cell culture supernatants by ELISA. CD4+ and CD8+ T cell responses, including proliferation and expression of cytokines and cytotoxic molecules were evaluated by flow cytometry. ChAdOx1 MERS induced marked spike-specific anti-MERS IgG antibody responses, which were significantly stronger than those induced by inactivated MERS-CoV. ChAdOx1 MERS also activated higher CD4+ and CD8+ T cell proliferative responses, cytokine expression (IFNγ, TNFα) by CD4+ T cells and cytotoxic perforin and granzyme B expression by CD8+ T cells than by inactivated MERS-CoV. Both antibody and T cell responses were shown stronger in adults than in children. There was a positive correlation between CD4+ T cell proliferation and the antibody response. Human NALT offers an efficient immune induction site for Spike-specific anti-MERS antibody and T cell response. Viral vectored ChAdOx1 MERS induces marked antibody and T cell responses in the NALT, supporting its potential as a mucosal (e.g. intranasal) vaccine against MERS.