Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

摘要

Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.