Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.
There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
Amy
A
Sexton
Robert
R
De Rose
Jeanette C
JC
Reece
Sheilajen
S
Alcantara
Liyen
L
Loh
Jessica M
JM
Moffat
Karen
K
Laurie
Aeron
A
Hurt
Peter C
PC
Doherty
Stephen J
SJ
Turner
Stephen J
SJ
Kent
John
J
Stambas
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005818:Genetic Engineering; D006678:HIV / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D008254:Macaca nemestrina; D023421:Models, Animal; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
D016915:AIDS Vaccines; D018449:SAIDS Vaccines