Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.
Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.
Malkevitch
Nina V
NV
Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, 41 Medlars Drive MSC 5065, Building 41, Room D804, Bethesda, MD 20892-5065, USA.
Patterson
L Jean
LJ
Aldrich
M Kristine
MK
Wu
Yichen
Y
Venzon
David
D
Florese
Ruth H
RH
Kalyanaraman
V S
VS
Pal
Ranajit
R
Lee
Eun Mi
EM
Zhao
Jun
J
Cristillo
Anthony
A
Robert-Guroff
Marjorie
M
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000285:Administration, Rectal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014766:Viremia; D014779:Virus Replication
D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic