An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS.
We explored the use of a simian-human immunodeficiency virus (SHIV) DNA vaccine as an effective mucosal priming agent to stimulate a protective immune response for AIDS prevention. Rhesus macaques were vaccinated rectally with a DNA construct producing replication-defective SHIV particles, and boosted with either the same DNA construct or recombinant modified vaccinia virus Ankara (MVA) expressing SIV Gag, SIV Pol, and HIV Env (MVA-SHIV). Virus-specific mucosal and systemic humoral and cell-mediated immune responses could be stimulated by this approach but were present inconsistently among the vaccinated animals. Rectal vaccination with either SHIV DNA alone or SHIV DNA followed by MVA-SHIV induced SIV Gag/Pol- or HIV gp120-specific IgA in rectal secretions of four of seven animals. However, the gp120-specific rectal IgA antibody responses were not durable and had become undetectable in all but one animal shortly before rectal challenge with pathogenic SHIV 89.6P. Only the macaques primed with SHIV DNA and boosted with MVA-SHIV demonstrated SHIV-specific IgG in plasma. In addition, these animals developed more consistent antiviral cell-mediated responses and had better preservation of CD4 T cells following challenge with SHIV 89.6P. Our study demonstrates the utility of a rectal DNA/MVA vaccination protocol for the induction of diverse responses in different immunological compartments. In addition, the immunity achieved with this mucosal vaccination regimen is sufficient to delay progression to AIDS.
Department of Medicine, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Shainn-Wei
SW
Wang
Frederic M N
FM
Bertley
Pamela A
PA
Kozlowski
Lara
L
Herrmann
Kelledy
K
Manson
Gail
G
Mazzara
Mike
M
Piatak
R Paul
RP
Johnson
Angela
A
Carville
Keith
K
Mansfield
Anna
A
Aldovini
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000285:Administration, Rectal; D000818:Animals; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic