Effects of different promoters on the protective efficacy of recombinant Marek’s disease virus type 1 expressing the VP2 gene of infectious bursal disease virus

The vaccine efficacy of recombinant viruses can be influenced by many factors. Accordingly, the activity of promoters has been one of the major factors affecting the antigen expression and protection rate. In the present study, two recombinant Marek’s disease virus type 1 (MDV1) vaccines containing the VP2 gene of infectious bursal disease virus (IBDV) under control of different promoters were generated from overlapping fosmid DNAs. The rMDV-Pec-VP2 virus containing the VP2 gene under control of the Pec promoter (CMV enhancer and chicken β-actin chimera promoter) demonstrated higher VP2 expression and stronger antibody response against IBDV in chickens than the rMDV-CMV-VP2 virus using the CMV promoter. After IBDV lethal challenge in specific-pathogen-free chickens, rMDV-Pec-VP2 provided complete protection against developing mortality, clinical signs, and the formation of bursal lesions, which was better than that provided by rMDV-CMV-VP2. Our findings indicate that the protective efficacy of the recombinant MDV1 vaccine against IBDV highly correlates with VP2 expression. This recombinant MDV1 vaccine expressing VP2 could have significant potential as a bivalent vaccine against both virulent IBDV and MDV infections in chickens.     

Heterologous priming–boosting with DNA and vaccinia virus expressing kinetoplastid membrane protein-11 induces potent cellular immune response and confers protection against infection with antimony resistant and sensitive strains of Leishmania (Leishmania) donovani

Background

Emergence of resistance against commonly available drugs poses a major threat in the treatment of visceral leishmaniasis (VL), particularly in the Indian subcontinent. Absence of any licensed vaccine against VL emphasizes the urgent need to develop an effective alternative vaccination strategy.

Methodology

We developed a novel heterologous prime boost immunization strategy using kinetoplastid membrane protein-11 (KMP-11) DNA priming followed by boosting with recombinant vaccinia virus (rVV) expressing the same antigen. The efficacy of this vaccination regimen in a murine and hamster model of visceral leishmaniasis caused by both antimony resistant (Sb-R) and sensitive (Sb-S) Leishmania (L.) donovani is examined.

Result

Heterologous prime-boost (KMP-11 DNA/rVV) vaccination was able to protect mice and hamsters from experimental VL induced by both Sb-S and Sb-R-L. (L.) donovani isolates. Parasite burden is kept significantly low in the vaccinated groups even after 60 days post-infection in hamsters, which are extremely susceptible to VL. Protection in mice is correlated with strong cellular and humoral immune responses. Generation of polyfunctional CD8⁺ T cell was observed in vaccinated groups, which is one of the most important prerequisite for successful vaccination against VL. Protection was accompanied with generation of antigen specific CD4⁺ and CD8⁺ cells that produced effector cytokines such as IFN-γ, IL-2 and TNF-α. KMP-11-DNA/rVV vaccination also developed strong cytotoxic response and reversed T-cell impairment to induce antigen specific T cell proliferation.

Conclusion

KMP-11 is a unique antigen with high epitope density. Heterologous prime boost vaccination activates CD4⁺ and CD8⁺ T-cell mediated immunity to confer resistance to VL. This immunization method also produces high quality T-cells secreting multiple effector cytokines thus enhancing durability of the immune response. Thus the vaccination regime as described in the present study could provide a potent strategy for future anti-leishmanial vaccine development.     

Brucella abortus S19 and RB51 vaccine immunogenicity test: Evaluation of three mice (BALB/c,Swiss and CD-1®) and two challenge strains (544 and 2308)

The aim of the present study was to evaluate the use of different mouse strains (BALB/c, Swiss and CD-1^®) and different challenge strains (Brucella abortus 544 and 2308) in the study of B. abortus vaccine (S19 and RB51) immunogenicity test in the murine model. No significant difference in B. abortus vaccine potency assay was found with the use of B. abortus 544 or B. abortus 2308 as challenge strain. Results of variance analysis showed an interaction between treatment and mouse strain; therefore these parameters could not be compared separately. When CD-1^® groups were compared, those vaccinated showed significantly lower counts than non-vaccinated ones (P < 0.05), independently of the vaccine received (S19 or RB51). Similar results were observed on BALB/c groups. However, in Swiss mouse groups, S19 was more protective than RB51 (P  <0.05), which showed protection when compared to the non-vaccinated group (P < 0.05). In summary, data from the present study showed that CD-1^®, BALB/c and Swiss mice strains, as well as both challenge strains, B. abortus strains 544 and 2308, can be used in immunogenicity tests of S19 and RB51 vaccines.