Application of Outer Membrane Vesicle of Neisseria meningitidis Serogroup B as a New Adjuvant to Induce Strongly Th1-Oriented Responses Against HIV-1

Mohammad      Reza Aghasadeghi; Ali      Sharifat Salmani; Seyed      Mehdi Sadat; Foozieh      Javadi; Arash      Memarnejadian; Rouhoullah      Vahabpour; Rezvan      Zabihollahi; Arfa      Moshiri; Seyed      Davar Siadat

Abstract

Despite the worldwide efforts made in the field of HIV vaccine development, an efficient AIDS vaccine strategy is still vague. Virus-like particles (VLPs) are one of the introduced aspects for HIV vaccine development since the non-replicative nature of HIV VLPs, resulting from the lack of viral genomic RNA, makes them suitable for broad applications. We have previously designed and introduced non-infectious VLPs (mzNL4-3) by introduction of a deletion mutation in the reverse transcriptase and integrase coding regions of HV-1. There are evidences suggesting that an effective cellular immune response against HIV-1 is able to control and suppress viremia during primary and chronic HIV infections. In the present study we have evaluated the potency of mzNL4-3 VLPs mixed with Neisseria meningitidis serogroup B outer-membrane vesicle (OMV), which is among the microbial components with proved adjuvant properties, to induce humoral and cellular responses against HIV-1. Analysis of anti-HIV-1 responses elicited in immunized BALB/c mice following different immunization regimens indicated OMV+VLP as an immunopotent combination which significantly induced anti-HIV-1 IgG with IgG2a dominancy. Results of cytokine and ELISpot assays also showed the capability of VLP+OMV immunogen for effective induction of IFN-gamma; and IL4 secreting cells and further suggested the promotion of Th1-oriented response that was evidenced with the increased IFN-γ/IL4 secretion ratio. According to our study, HIV-1 VLPs combined with N. meningitidis B OMVs seem to be a promising approach in vaccine development against HIV-1.

Keywords: HIV-1, VLP, Neisseria meningitidis, OMV, Cell mediated immunity, Th 1, antigens, HBsAg, Virus Like Particles, Cytokine