Abstract
Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER) from human immunodeficiency virus type 1 (HIV-1) within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.
Highlights
human immunodeficiency virus type 1 (HIV-1) is predominantly transmitted at mucosal surfaces, but vaccine design and evaluation have focused primarily on systemic immune responses
Chromosomal DNA was analyzed by PCR using primers that were either specific to sequences flanking the replaced region or specific to the inserted membrane proximal external region (MPER)-encoding sequence (S1 Fig)
S-layer proteins may be a more efficient means to display specific vaccine epitopes as compared to other surface display approaches such as LPXTG-anchored proteins and flagella [14,31,32]
Summary
HIV-1 is predominantly transmitted at mucosal surfaces, but vaccine design and evaluation have focused primarily on systemic immune responses. The mucosal immune system is, in many respects, independent of the systemic immune system. 90% of intestinal and 50% of vaginal IgA is produced locally and induction of mucosal immunity is best achieved via mucosal infection or vaccination [1,2,3]. Passive transfer studies using broadly neutralizing antibodies (BnAb) have shown protection against mucosal transmission (reviewed in [4]). Induction of BnAb has proven extraordinarily difficult because neutralizing epitopes are often structurally complex and difficult to faithfully recapitulate, long-term immune maturation is needed to acquire the extensive hypermutation described for most neutralizing IgG, and some.
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