Effects of adjuvants on IgG subclasses elicited by virus-like Particles

<p>Abstract</p> <p>Background</p> <p>Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model.</p> <p>Results</p> <p>Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced T_H2 pattern, VLPs formulated with either adjuvant elicited a T_H1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826.</p> <p>Conclusions</p> <p>The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.</p

Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T cell response while enhancing antibody response

<p>Abstract</p> <p>Background</p> <p>The binding of Abs to the CD4-binding site (CD4bs) of HIV-1 envelope gp120 has been shown to obstruct the processing and generation of helper epitopes from this antigen, resulting in poor presentation of various gp120 epitopes by MHC class II to CD4 T cells. However, the physiologic significance of these inhibitory anti-CD4bs Abs <it>in vivo </it>has remained unclear. In this study, we evaluated the immunologic effects of anti-CD4bs Abs <it>in vivo </it>using a murine model.</p> <p>Results</p> <p>Animals were immunized with recombinant envelope proteins with or without CD4-binding activity (designated CD4bs⁺Env and CD4bs^–Env, respectively). As expected, anti-CD4bs Abs were generated only after immunization with CD4bs+ Env and not with CD4bs^–Env. The presence of anti-CD4bs Abs was associated with lower levels of envelope-specific lymphoproliferation in animals immunized with CD4bs+ Env. To further determine the specific role of the anti-CD4bs Abs, we immunized mice with gp120 in the presence of an inhibitory anti-CD4bs mAb or a non-inhibitory anti-gp120 mAb. The data show that the presence of anti-CD4bs mAb reduced CD4 T cell responses to gp120. However, we also detected significantly higher titers of anti-gp120 Abs following immunization with gp120 and the anti-CD4bs mAb.</p> <p>Conclusion</p> <p>Anti-CD4bs Abs can exert discordant effects on the gp120-specific CD4 T cell and Ab responses <it>in vivo</it>, indicating the importance of these particular Abs in influencing both the cellular and the humoral immune responses against HIV-1.</p

A Compensatory Liability Regime to Promote the Exchange of Microbial Genetic Resources for Research and Benefit Sharing

Female rhesus macaques were immunized with HIV virus-like particles (HIV-VLPs) or HIV DNA administered as sequential combinations of mucosal (intranasal) and systemic (intramuscular) routes, according to homologous or heterologous prime-boost schedules. The results show that in rhesus macaques only the sequential intranasal and intramuscular administration of HIV-VLPs, and not the intranasal alone, is able to elicit humoral immune response at the systemic as well as the vaginal level.funding agencies|Simian Vaccine Evaluation Unit (SVEU) of the Division of AIDS||European Community|201433|</p