Mucosal Immunity Induced by Intramuscular Administration of Free Peptides In‐Line with PADRE: IgA Antibodies to the ELDKWA Epitope of HIV gp41

Abstract

To improve the mucosal antibody response against a short amino acid (aa) sequence (ELDKWA) of HIV gp41, we have investigated a construction including this peptide in-line with the Pan DR epitope (PADRE). ELDKWA is a conserved peptide playing a key role in the pathogenicity of HIV transmission. PADRE is a non-natural peptide with multipotential immunogenic properties. The results show striking differences between mucosal and systemic immune systems, with a preferential response of the mucosal organs. In contrast with most mucosal immunizations, the intracellular response persists for over two months after the last injection. This strongly suggests that further investigations of conserved key epitopes from various pathogens may lead to safe and chemically defined mucosal vaccines with synthetic peptides. These candidate vaccines with free peptides may be suitable for mass campaigns even in developing countries.

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

“…Recently, we obtained an Ab response in the mucosal organs by i.m. injection of a synthetic fusion peptide containing ELDKWA and PADRE (12). Interestingly, we showed that this mucosal immune response persists for a long time after the booster injection (11,12).…”

“…A consensual epitope (p145) of the streptococcal protein M served as a negative control. These five peptides were extended with a C terminus cysteine residue used to branch six chains to OVA by disulfide bridging, as already described (11,12). This construct maintains the branched peptides under a native form necessary for ELISA and for inhibition studies.…”

“…of the washing. The relative level (in arbitrary units) was defined as the ratio of Ab activity to the concentration of total Ig (12). Because of their low levels, the IgG Abs were expressed only by OD values.…”

“…We investigate two mucosal adjuvants, since we have already observed that Alum, the most commonly used systemic adjuvant, exerts an inhibitory effect on this response (12). We show that these adjuvants, CT and CpG, also suppress the response and are therefore not suitable for this immunization.…”

Parenteral Vaccination Can Be an Effective Means of Inducing Protective Mucosal Responses

“…Studies using murine or other small-laboratory-animal models have also provided relevant, although at times inconclusive, evidence of mucosally committed responses after parenteral delivery of vaccines (11)(12)(13)(14)(15). A few important examples include reports of long-lasting mucosal IgA responses in intestinal tissues of BALB/c mice after intramuscular injection of nonadjuvanted tetanus toxoid (TT) and persistent levels of intestinal and vaginal antibodies after intramuscular immunization of mice with an HIV gp41 peptide mixed with a major histocompatibility complex class II (MHC-II) binding peptide.…”