[Show abstract][Hide abstract] ABSTRACT: In an earlier study, we provided strong evidence that liposomes made of sperm membrane lipids (spermatosomes) can deliver entrapped molecules to the cytosol of target cells. Now we have evaluated the immunological behavior of spermatosome-encapsulated soluble antigen ovalbumin (OVA) in BALB/c mice. Spermatosome-mediated antigen delivery can affect both cytosolic and endosomal antigen-processing pathways, simultaneously, leading to the generation of CD4+ T-helper and CD8+ cytotoxic T-cell responses. Isotype studies revealed that immunization with spermatosome-encapsulated OVA elicits mainly IgG2a and IgG1 subclasses of antibodies. A potential vaccine candidate should impart long-lasting protection against infection; to this end, immunization with spermatosome-encapsulated OVA resulted in expression of CD44 and CD62L cell-surface markers on T cells, suggestive of a desirable memory response. We conclude that spermatosome encapsulation is a useful strategy for vaccine production, because it enhances the immunological activity of the encapsulated antigen.