Evaluation of fowlpox–vaccinia virus prime-boost vaccine strategies for high-level mucosal and systemic immunity against HIV-1

• Published in: Vaccine 2006-07, Vol.24 (31), p.5881-5895
• Main Authors: Ranasinghe, Charani, Medveczky, Jill C., Woltring, Donna, Gao, Ke, Thomson, Scott, Coupar, Barbara E.H., Boyle, David B., Ramsay, Alistair J., Ramshaw, Ian A.
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS Vaccines - immunology; AIDS Vaccines - therapeutic use; Animals; Antigens; Applied microbiology; Biological and medical sciences; Co-stimulatory molecules; Drug Evaluation, Preclinical - methods; Fowlpox virus; Fowlpox virus - immunology; Fundamental and applied biological sciences. Psychology; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1 - immunology; Human immunodeficiency virus 1; Immune response; Immune system; Immunity, Mucosal - immunology; Immunization, Secondary - methods; Immunodominance; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mucosal immunity; Oral/intranasal rFPV delivery; Peptides; Poxvirus; Prime-boost; T cell receptors; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccinia virus; Vaccinia virus - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.04.023

We have tested the efficacy of recombinant fowl pox (rFPV) and recombinant vaccinia virus (rVV) encoding antigens of AE clade HIV-1 in a prime-boost strategy, using both systemic and mucosal delivery routes. Of the various vaccine routes tested, intranasal/intramuscular (i.n./i.m.) AE FPV/AE VV prime-boosting generated the highest mucosal and systemic T cell responses. Peak mucosal T cell responses occurred as early as 3 days post-boost vaccination. In contrast only low systemic responses were observed at this time with the peak response occurring at day 7. Current data also revealed that, due to better uptake of the rFPV, intranasal viral priming was much more effective than intranasal rDNA priming tested previously. The i.m./i.m. prime-boost delivery also generated strong systemic but poor mucosal responses to Gag peptides. Interestingly, the oral administration of AE FPV followed by i.m. AE VV delivery elicited strong systemic responses to sub-dominant Pol 1 peptides that were absent in mice that received vaccine by other routes. Moreover, priming with AE FPV co-expressing cytokine IL-12 significantly enhanced the T cell responses to target antigens, whilst co-expression of IFNγ decreased these responses. The results also indicated that the route of inoculation and the vaccine vector combination could radically influence not only the magnitude but also the antigen specificity of the immune response generated. Further, in contrast to the generally protracted HIV rDNA/rFPV multiple delivery prime-boosting, this single rFPV prime and rVV boost approach was more flexible and generated excellent mucosal and systemic immune responses to HIV vaccine antigens.