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

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.

Contribution of factor H-Binding protein sequence to the cross-reactivity of meningococcal native outer membrane vesicle vaccines with over-expressed fHbp variant group 1

“…An important consideration in relation to this is the presentation of antigens on NOMV in a more native environment and native conformation, compared to recombinant proteins, so that the epitopes on the NOMV vaccines better resemble those of the bacterium. Moreover, the intrinsic adjuvanticity of outer membrane vesicles is also relevant [44, 45]: the immune response against protective antigens on NOMV is likely to be enhanced due to the stimulation of innate receptors (e.g. TLR2 by PorB, TLR4 by LOS [46, 47]), and may also be affected by a different balance in IgG subtype induced by NOMV OE fHbp, compared to the recombinant protein [48].…”

Proteomic Analysis and Immunogenicity of Mannheimia haemolytica Vesicles

“…Moreover, bacterial vesicles have been successfully used as vaccines or components of vaccines in pathogenic bacteria, including Vibrio cholerae (30), the oral (36,37). Bacterial vesicle vaccines, however, are not uniformly efficacious in that meningococcal vesicles conjugated with capsular polysaccharide are weak immunogens in infants and neonatal mice (38).…”

Immune modulation by bacterial outer membrane vesicles

“…When introduced into the body, OMV antigens are presented by antigenpresenting cells (APCs) to CD4 + T cells 45,70,81,82 , which leads to the generation of antigen-specific B cell responses 45,78,82,83 . OMVs can induce protective immune responses during infection with a variety of pathogens -including V. cholerae 81 , H. pylori 80 , S. Typhimurium 45 and Shigella flexneri 84 -and this decreases bacterial burdens [85][86][87] and protects mice from sepsis or death 25,77,79,84,88 (TABLE 1).…”

“…OMVs are highly stable when exposed to different temperatures and treatments 111 , they are non-replicative and hence safe, and they contain many of the immunogenic surface-associated and membrane-associated components of their parent bacterium 45,90,99,112,113 . Furthermore, the ability of OMVs to activate the innate immune system 14,20,22,24,25,69,114 , together with their particulate nature, provides these nano particles with their own adjuvant activity, as they are able to enhance antibody and T cell responses to antigens 76,83,87,115 . Finally, OMVs are very versatile as they can be bioengineered to express any chosen antigen 77,112,[116][117][118] and they can be manipulated to reduce their endotoxicity [119][120][121] .…”