Priming-Boosting Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and a Nonreplicating Vaccinia Virus Recombinant Leads to Long-Lasting and Effective Immunity

Abstract

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-␥) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-␥ activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

“…BCG antigen stimulated splenocytes from non-immunized mice (38 +/− 17 pg/mL) had similar level of IL-1β compared to mice immunized with BCG/ lactoferrin (44 +/− 21 pg/mL); production of IL-1β was significantly decreased in splenocytes from the BCG immunized group (24 +/− 13 pg/mL) compared to the BCG/lactoferrin group. TB vaccines are useful when given as a one time injection or when administered using various schedules of prime-boost protocols [10,14,15,[43][44][45][46][47][48][49]. The next experiments examined the BCG/lactoferrin saline immunization protocol to generate protection against MTB infection when mice were immunized once (Protocol C), or when boosted prior to infection (Protocol D).…”

Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virusgag/pol

“…Because SHIV89.6 does not induce both a marked decline in CD4 ϩ cells and a high level of plasma viral load in cynomolgus macaques, we passaged serum from virus-infected cynomolgus macaques. The variant was obtained by the serum passages using cynomolgus macaques inoculated with SHIV89.6, and it induced high levels of viremia (1-10 ϫ 10 7 viral RNA copies/ml) and marked CD4 ϩ T cell depletion (Ͻ10 cells/l) within 2 and 3 wk after viral inoculation (30,31,39). Furthermore, genomic study revealed 16 mutations of genomic DNA and 15 amino acid mutations in the Env region of parental virus.…”

Double Oral Administration of Emtricitabine/Tenofovir Prior to Virus Exposure Protects against Highly Pathogenic Simian/Human Immunodeficiency Virus Infection in Macaques

“…Plasma viral loads were evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR) with a TaqMan probe as reported previously (19)(20)(21)(22)(23). Briefly, viral RNA was extracted from the plasma and purified using the QIAamp Viral RNA Mini Kit (Qiagen, Valencia, Calif., USA).…”

“…SHIV-KS661c can infect cynomolgus monkeys both intravenously and intra-rectally. The virus induces precipitous viremia and drastic CD4 cell depletion within 2 weeks of inoculation (19)(20)(21)(22)(23)(24)(25)(26). SHIVKS661c stocks were kept at -809 C and were thawed immediately prior to use.…”

“…The absolute CD4 cell count in peripheral blood (PB) was measured as described previously (19)(20)(21)(22)(23). Briefly, 50 ml of whole blood was incubated with FITC-conjugated monoclonal anti-CD3 (FN18; Biosource, Camarillo, Calif., USA), phycoerythrin-conjugated anti-CD4 (Leu-3a; Becton Dickinson, Franklin Lakes, N.J., USA), or peridinin chlorophyll protein-conjugated anti-CD8 (Leu-2a; Becton Dickinson).…”