Immunogenicity and safety of an Entamoeba histolytica adjuvanted protein vaccine candidate (LecA+GLA-3M-052 liposomes) in rhesus macaques

溶组织内阿米巴佐剂蛋白候选疫苗(LecA+GLA-3M-052脂质体)在恒河猴中的免疫原性和安全性

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作者:Mayuresh M Abhyankar, Feifan Xu, Deborah Chavez, Anna Goodroe, Elda Mendoza, Christopher Chen, Dhiraj K Singh, Fernando Varnador Jr, Sandra J Sivananthan, Robert Kinsey, William R Lykins, Brynn M Murphy, Andrew R Martin, Mark A Tomai, Soutik Ghosal, Corey Casper, Karl Pedersen, William A Petri Jr, C

Abstract

Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.

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