Therefore, an ideal Zika vaccine should induce robust antibody and T cell responses. Several studies demonstrate that CD4 and CD8 T cells play a critical role to mediate protection against Zika virus infection ( 12– 14). However, T cells are an important arm for the host to defend viral infections. These results suggest that antibodies alone were able to protect Zika virus infection. These results indicate that the induction of mucosal immunity is also important for novel Zika vaccine design.Īdoptive transfer of purified IgG from immunized mice provided passive protection, and depletion of CD4 and CD8 T cells in immunized mice did not abolish this protection ( 11). Many clinical studies have shown the presence of Zika virus RNA in the semen, vagina and cervix as well as vaginal and endocervical mucosa of infected patients ( 5, 9, 10). Recently, several reports have indicated that Zika virus can also be transmitted through sexual contact ( 7– 9). The primary route of Zika virus transmission is well known to occur through the bite of infected Aedes species mosquitoes ( 5, 6), primarily Aedes aegypti and Aedes albopictus. The development of effective mucosal vaccines that protect mucosal sites is needed ( 1– 4). However, only limited mucosal vaccines are currently available for human use. It is believed that mucosal immunity plays an important role in the first line of defense against pathogen invasion. Commonly vaccinated routes, including subcutaneous, intradermal, or intramuscular injection, can induce protective systemic antibodies but exhibit weaker responses in the induction of substantial mucosal antibodies ( 1). For example, infection of influenza virus, severe acute respiratory syndrome coronavirus, Vibrio cholerae, and herpes simplex virus. Several infections start on mucosal surfaces.
These results suggest that antigen-FLIPr fusion protein alone via intranasal administration can be applied to mucosal vaccine development.
Furthermore, we employed immunodeficient AG129 mice as a Zika virus infection model and demonstrated that intranasal administration of recombinant Zika virus envelope protein domain III-FLIPr fusion protein induced protective immune responses against the Zika virus. Importantly, activation of OVA-specific CD4 + and CD8 + T cells and induction of a broad-spectrum cytokine secretion profile were detected after intranasal administration of rOVA-FLIPr alone in immunocompetent C57BL/6 mice. Subsequently, OVA-specific IgG and IgA antibodies in the circulatory system and IgA antibodies in mucosal tissue were detected. Our results demonstrate that intranasal administration of recombinant OVA-FLIPr fusion protein (rOVA-FLIPr) alone efficiently delivers OVA to DCs in nasal lymphoid tissue. We employed formyl peptide receptor-like 1 inhibitory protein (FLIPr), an FcγR antagonist secreted by Staphylococcus aureus, as a vector to target ovalbumin (OVA) to dendritic cells (DCs) via intranasal administration.
Ming-Shu Hsieh 1, Chia-Wei Hsu 1, Ling-Ling Tu 1, Kit Man Chai 1, Li-Lu Yu 1, Chiao-Chieh Wu 1, Mei-Yu Chen 1, Chen-Yi Chiang 1, Shih-Jen Liu 1,2,3, Ching-Len Liao 1 and Hsin-Wei Chen 1,2,3*
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