• Vaccine Name: BCG auxotroph expressing HIV-1 clade immunogen
• Target Pathogen: Mycobacterium tuberculosis
• Target Disease: Tuberculosis
• Vaccine Ontology ID: VO_0004122
• Type: Live, attenuated vaccine
• Antigen: HIVA, an African HIV-1-derived immunogen, was identified as stable and inductive of HIV-1-specific CD4+ and CD8+ T cell responses. HIVA in this study contained an immunodominant H-2D^d restricted epitope P18-I10 (Im et al., 2007).
• Preparation: HIVA gene with mAb tag Pk was fused to M. tuberculosis 19-kDa lipoprotein signal sequence via PCR to improve foreign protein immunogenicity. HIVA was cloned into two plasmids, pJH222 and pJH223, as HindIII-HindIII fragment and used to transform a lysine auxotroph of BCG (BCG Pasteur lysA5::res). Additional preparations included MVA.HIVA and BCG.p. BCG cultures were grown in presence of kanamycin. HIVA immunogenicity was assessed using H-2D^d-restricted epitope P18-I10 and subdominant H-2K^d-restricted P epitope. MHC class II-restricted responses were tested using three epitope peptides derived from p24 (Im et al., 2007).
• Description: Goal of study was to develop a vaccine to minimize the risk of mother-to-child transmission (MTCT) of M. tuberculosis and HIV-1, and to protect against both pathogens in newborns. BCG was selected as a vaccine vector due to its long efficacy as a vaccine (10-15 years), frequent use in infant and newborn vaccination, and induction of humoral and cellular responses (Im et al., 2007).

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were immunized on day 0 with either BCG.HIVA (pJH222.HIVA) and episomal plasmid, parental BCG (BCG.p), or control (no immunization). Half of the animals were boosted with MVA.HIVA on day 102. Mice were sacrificed on day 151. T cells were stimulated with peptides in a multicolor flow cytometric analysis to elicite interferon gamma, tumor necrosis factor alpha, and degranulating responses (Im et al., 2007).
• Immune Response: HIVA-specific responses peaked after 12 weeks, most likely as a result of BCG-induced activation of T cells. Three major observations were observed:
  1) BCG.HIVA alone induces undetectable CD8+ HIV-1-specific T cell responses secreting tum, though priming with BCG.HIVA shows significant increases in elicited H and P-specific splenocytes producing IFN-gamma and degranulating. Hence, BCG.HIVA enhancement of MVA.HIVA responses is HIVA-specific.
  2) BCG.HIVA priming with MVA.HIVA boost elicits the highest proportion of HIV-1 specific bifunctional cells in all the studies.
  3) No HIVA-induced CD4+ T cell responses were detected (Im et al., 2007).
• Information about this animal model: Mouse Model for TB research

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were primed with increasing doses (10^3-10^7 CFU/animal, day 0) of BCG.HIVA or not vaccinated, and boosted (day 102) with constant doses of MVA.HIVA.
• Immune Response: Bifunctional responses increased steadily with dose up to 0.7% CD8+ splenocytes with 10^6 CFU BCG.HIVA for epitope H , and increased up to 0.2% CD8+ with 10^7 CFU for P response (Im et al., 2007). Priming dose of BCG.HIVA affects strength and quality of CD8+ T cell responses induced by the recombinant BCG priming followed by recombinant MVA boosting, with high priming dose being most important for quality of response to P epitope (Im et al., 2007).
• Information about this animal model: Mouse Model for TB research

Mouse Response

• Host Strain: BALB/c, 6-8 wk old
• Vaccination Protocol: Pathogen free mice were vaccinated in groups of 7-9 animals with 3x10^5 CFU of BCG.HIVA, BCG.p, or BCG wild type 1173 p2 via s.c. injection into left hind foot.
• Challenge Protocol: Mice were challenged via aerosol (nasal) route 12 weeks post-vaccination with M. tuberculosis Erdman using a modified Henderson apparatus. Approximately 25 CFU/lung were estimated 24 hours post-challenge (Im et al., 2007).
• Efficacy: All three vaccines tested here showed an approximate 2-fold reduction in M. tuberculosis load in the lungs and spleen. Data suggest that the "safer" lysine auxotrophBCG.HIVA could replace BCG vaccine in neonatal uses and still show comparable efficacy (Im et al., 2007).
• Information about this animal model: Mouse Model for TB research

Mouse Response

• Host Strain: BALB/c, female
• Vaccination Protocol: Groups of 4-5 mice were naive or immunized with 100 μg pTHr.HIVA, 10^6 pfu MVA.HIVA, or 10^6 cfu of either BCG.p or BCG.HIVA. BCG.HIVA boosting commenced on day 33.
• Immune Response: No HIVA-specific responses were noticed during the 4-day WR.HIVA infection. Mice receiving the pTHr.HIVA-BCG.p, pTHr.HIVA-BCG.HIVA , or BCG.HIVA showed both H and P specific responses. Highest responses were seen in pTHr.HIVA-BCG.HIVA-WR.HIVA which showed interferon gamma and degranulated responses. CD4+IFN-gamma+TNF-alpha+IL-2+ splenocytes exhibited high quality characteristics in the BCG.HIVA and BCG.p boosts following pTHr.HIVA priming. HIVA non-specific mechanisms were suggested by a two-log10 decrease in WR.HIVA titre when BCG.HIVA or BCG.p alone were used in immunization (Im et al., 2007).
• Challenge Protocol: Mice were challenged i.p. using 4x10^6 pfu vaccinia virus WR.HIVA. Plaque counts were determined for sonicated and serially-diluted mouse ovaries four days post-challenge (Im et al., 2007).
• Description: Surrogate challenge with recombinant replication-competent vaccinia virus (strain Western Reserve) is a cost-effective murine alternative to HIV-1challenge in non-human primate models.
• Information about this animal model: Mouse Model for TB research