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.

Brucellosis is a worldwide zoonosis and represents one of the most important public health problems in many countries, especially around the Mediterranean basin, Middle East, India and Central and South America. Currently subunit vaccines are being considered to develop effective vaccines for human which has been evidenced by vaccines currently available against the infections such as meningococcal diseases and influenza .The application of new adjuvants of microbial origins is also underway to design subunit vaccines promoting the immune responses to the antigenic determinant(s) of the vaccine. In order to explore the efficacy of Brucella abortus lipopolysaccharide (LPS) combined with different adjuvants and proteins (as a vaccine candidate) in the induction of immune response as an effective and long-lasting immunity against Brucella, we evaluated the outer membrane vesicle of Neisseria meningitidis serogroup B (GBMOMV) as a subcutaneous adjuvant and a part of a brucellosis candidate vaccine to induce high titres of specific anti-Brucella abortus S99 LPS in animal model (mice). The obtained results were compared with complete and incomplete Freund's adjuvants (CFA and IFA). LPS+GBMOMV was the most immunogenic compound that stimulated following the first injection an increase in IgG titre of about 3.90, 3.18 and 1.58 fold higher than that produced against LPS, LPS+IFA and LPS+CFA, respectively. The highest anti-LPS IgG titre was detected two weeks after the third injection (the day 42) of LPS+GBMOMV. Purified GBMOMV can be considered as a safe subcutaneous adjuvant and a part of a candidate vaccine when combined with lipopolysaccharide of Brucella abortus S99.

Problem statement: Brucellosis is a globally found infectious disease and there is no licensed vaccine against human brucellosis. The present study carried-out to evaluate the potency of our modified extracted lipopolysaccharide (LPS) of B. abortus to elicit specific anti-Brucella antibodies in animal model (Rabbit) as a part of a candidate vaccine for brucellosis. Lipopolysaccharide is one of the main virulence factors and the most immunogenic structure of smooth strains of Brucella. Approach: Lipopolysaccharide of B. abortus S99 (S-LPS) initially extracted through an optimized method as described previously. After biochemical and pyrogenicity evaluations of the extracted S-LPS humoral immune response against the extracted LPS analyzed in animal model through serological assays such as Rose Bengal assay, Rapid agglutination (Rapid Wright) test and Standard agglutination test (SAT or Wright test) to demonstrate the specific elicited antibodies against the injected LPS. In addition, the interaction of LPS and anti-LPS antibodies was demonstrated by Agarose Gel Immunodiffusion (AGID) assay. Results: Higher doses of B. abortus S99 LPS caused less or equal body temperature increase in comparison to E. coli LPS doses. Sera of immunized animals had been reported positive by RBT because of B. abortus LPS immunogenicity which we extracted through our optimized method. The highest titer of anti-Brucella antibodies detected two weeks after the third immunization (assayed by rapid slide agglutination and standard agglutination tests). Anti-Brucella antibodies of immunized animals reacted more specifically with the LPS of B. abortus in comparison with E. coli LPS and precipitation lines between B. abortus LPS and immune sera appeared after 30 min while detected after three hours for E. coli LPS. Conclusions/Recommendations: The properties of B. abortus S99 LPS concluded from the present study results, suggest the possible use of this component as a carrier or a part of a sub-unit or conjugated vaccine for human brucellosis.

Neisseria meningitidis is efficiently phagocytosed by polymorphonuclear leukocytes (PMN S ) following opsonization with opsonic antibodies; opsonophagocytosis is the primary mechanism for clearance of meningococci from the host. Thus, in testing meningococcal vaccines, the level of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. Our previous studies demonstrated that the conjugation of N. meningitidis serogroup A capsular polysaccharide (CPSA) to serogroup B outer membrane vesicle (OMV) could induce a high level of bactericidal antibody response against serogroup A meningococci in animals. The purpose of this study was to evaluate opsonophagocytic activity of the conjugate of CPSA to OMV (CPSA-OMV). In order to evaluate the potential efficacy of CPSA-OMV a flow cytometric opsonophagocytic assay was used. The conjugate and controls were injected intramuscularly into four groups of rabbits with boosters on days 14, 28 and 42 following primary immunization. The rabbits were bled prior to injection and two weeks after each injection. Opsonophagocytic activity of antibodies in hyperimmune sera through rabbit PMN S were measured with flow cytometer, using dihydrorhodamine-123 as a probe. The results indicated that our conjugate could induce a highly significant level of opsonophagocytic activity against serogroup A meningococci after 56 days compared to the control groups (P<0.05). We conclude that this conjugate represents a vaccine candidate against serogroups A and B meningococci after further investigation.