[Properties of mucosal antibodies]. / Propriétés des anticorps des muqueuses.

Mucosal antibodies consist of a variety of molecules, including secretory IgA and local IgG, involved in the first immune barrier of defence against pathogens. They account for the majority of daily synthesized immunoglobulins in the body and mostly depend on the secretory immune system which is independent from its systemic counterpart. Acting by immune exclusion and immune elimination, these immunoglobulins correspond to preimmune poly-reactive natural antibodies and to antigen-induced antibodies. Recent progress in this field have suggested new approaches of mucosal vaccines preventing the entry of pathogens in the body.

Induction of a mucosal immune response to the streptococcal M protein by intramuscular administration of a PADRE-ASREAK peptide.

In a previous study, it was shown that an intramuscular administration of amino acid PADRE-ELDKWA sequence induced a mucosal immune response to a conserved epitope of human immunodeficiency virus in mice. In the same model, here it is shown that this method can be used with a selected peptide from the M protein of group A streptococci. The PADRE-ASREAK sequence was injected in mice by the intramuscular route. Antibodies against M protein were detected in extracts of mucosal tissues and in serum. The repertoire isotypes of serum immunoglobulin G (IgG) and mucosal IgA and IgG antibodies varied, according to the dose of injected peptide. The highest mucosal IgA antibody response was obtained with 0.01 micro g of antigen per injection, whereas the systemic IgG antibody response increased with 10 micro g of antigen. Mucosal antibody production against streptococci was confirmed by immunofluorescence analysis. These results provide evidence that this novel approach of mucosal vaccination may be of advantage for bacterial systems and suggest a new field of investigation based on synthetic peptide analogues.

Mucosal immunity induced by intramuscular administration of free peptides in-line with PADRE: IgA antibodies to the ELDKWA epitope of HIV gp41.

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.

Induction in mucosa of IgG and IgA antibodies against parenterally administered soluble immunogens.

The induction of a mucosal immunity provides an additional principle of vaccination by preventing the entry of pathogens in the body. Albeit the fact that intensive research has been conducted on local vaccines, the major mucosal vaccine commercially available for human use remains the oral polio vaccine. We have previously demonstrated that parenteral vaccination in humans with tetanus toxoid (TT) results in a genital immunoglobulin (Ig)G antibody (Ab) response. Here, we show that injections of TT with no adjuvant induces an anti-TT response in the mucosal tissues of normal BALB/c mice. The response is multiregional, involves both IgG and IgA isotypes, and is long-lasting. Similarly, injections of haptens coupled to TT or to other diffusible proteins may induce mucosal Abs. These results led us to immunize normal BALB/c mice with a viral peptide coupled to TT by disulfide bridging. The hapten was a 17 amino acid peptide containing the ELDKWA sequence of human immunodeficiency virus (HIV)-1 gp41. A significant IgG and IgA Ab response to the immunizing peptide was induced in various mucosal tissues despite the presence of a suboptimal Ab response in the spleen. The results indicate that mucosal immunity to peptides that are candidates for human vaccinations may be achieved by parenteral adjuvant-free immunization with peptide coupled to TT.