Oral administration of a self-assembling nanofiber-based vaccine generates neutralizing antibodies against HIV and expands CD8+ memory T cell populations

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Abstract Human immunodeficiency virus (HIV) is the world’s sixth leading cause of death. Antiretroviral therapy (ART) is the current standard of treatment, but issues of accessibility and compliance pose additional hurdles. In 2018, there were 37.9 million people living with HIV, but only 62% were on ART. The development of a successful vaccine is imperative to combat the transmission of HIV, of which one of the major goals is to generate broadly neutralizing antibodies (bnAb). The membrane-proximal external region (MPER) of gp41 in the envelope glycoprotein (Env) is a largely conserved motif, a key player in fusion, and the target of bnAb in a subset of patients with long-term HIV infections. We previously demonstrated the efficacy of a nanofiber vaccine platform as evidenced by the generation of both strong humoral and cell-mediated responses against viral targets, and enhanced protection against infection. In recent studies, we observed that serial oral dosing of nanofibers (NF) bearing the MPER epitope (NF-MPER) in mice correlated with a significant increase in serum and mucosal neutralizing antibodies against HIV. The NF-MPER vaccine also augmented CD8+ memory T cell populations in the colon, which were further characterized as effector memory T cells (TEM), using surface marker phenotypes (CD69+/− CD103+ CD44+ CD62Llo). Additionally, we observed significant expansion of CD8+ TEM pools in the spleen, a reservoir for HIV, a subset of which were similar to tissue resident memory T cells (TRM) seen in human elite controllers. These results suggest that oral immunization with a NF-based vaccine elicits the production of bnAb and enhanced CD8+ TEM populations, in non-lymphoid and lymphoid tissues, that are necessary for a successful HIV vaccine.