Molecular analysis of the modulatory factors of the response to HBsAg in mice as an approach to HBV vaccine enhancement

Abstract

Mice were injected with immune complexes containing the recombinant hepatitis B surface antigen (HBsAg) vaccine (S + preS2) bound to different monoclonal antibodies (mAbs), in order to determine whether an enhancement of the response to a human vaccine could be obtained and observed. Enhancement and indifference were observed, as well as a decrease in immunogenicity. No relationship could be established between any effect and affinity or isotype of the bound mAbs. The preS2 region was rendered more immunogenic when an IgG2a mAb was bound to the S region of the HBsAg. The response to the S region was not modulated, whereas immunogenicity of the preS2 colinear region was decreased by antibody shielding. The mAb which was the most efficient as an enhancer of the antibody response also increased binding of the complexed immunogen to antigen presenting cells. The binding of a human mAb to the sole S region, but not to the preS2 region, should be tested as a potentiating agent of the anti-preS2 human immune response.

Antibody-Mediated Immunomodulation: a Strategy To Improve Host Responses against Microbial Antigens

“…As stated earlier, immunization with IC containing certain MAbs and HbsAg resulted in the formation of antibodies directed against novel epitopes of the vaccine immunogen (16). This finding may be of direct clinical applicability, considering the relatively high percentage of individuals who do not seroconvert following immunzation with HBsAg alone (22) in that additional target epitopes would be available and potentially recognizable by the nonresponding population.…”

“…For example, the pre-S2 region of hepatitis B surface antigen (HbsAg) was rendered more immunogenic when a MAb was bound to the S region of the HbsAg. Not all antiHbsAg MAbs resulted in enhancement of the response, and indifference or negative modulations could also be demonstrated depending on the selection of the MAb (16).…”

“…Secondary responses were enhanced approximately threefold following boosting with IgG2-complexed antigen rather than free antigen. In a series of studies, Bouige et al demonstrated that immunization with IC containing MAbs and several different types of antigens, including human secretory IgA (sIgA), bacterial polysaccharide from Escherichia coli, and a structural protein from hepatitis B virus, could result in the recognition of new epitopes that differed in location from those recognized by the modulating MAbs (15)(16)(17). For example, the pre-S2 region of hepatitis B surface antigen (HbsAg) was rendered more immunogenic when a MAb was bound to the S region of the HbsAg.…”

“…However, the benefit of utilizing antibody in combination with antigen to achieve a desirable immune response is far less appreciated and is the focus of this minireview. There is increasing recognition that exogenously administered antibody may exert a therapeutic effect by redirecting the host response rather than by playing a purely passive role (16,18,26,45,53,55,56,84,90,93,100,114,129). Both polyclonal and monoclonal reagents, administered either alone or in combination with antigen, have been used to up-regulate beneficial or protective immune responses against infectious agents and malignant tumors as well as to down-regulate deleterious responses associated with inflammation, autoimmunity, and hypersensitivity (8,55,57,58,84,102,110).…”

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

“…In addition, however, antibodies in ICs can also exert epitopespecific effects and modulate the specificity of the antibodies induced. Mechanisms such as epitope shielding or antibodymediated conformational changes have been proposed to explain the phenomena observed (28,38,44,45).…”