Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge.
Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection.
Mattapallil
Joseph J
JJ
Vaccine Research Center, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Douek
Daniel C
DC
Buckler-White
Alicia
A
Montefiori
David
D
Letvin
Norman L
NL
Nabel
Gary J
GJ
Roederer
Mario
M
D000818:Animals; D000956:Antigens, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D007156:Immunologic Memory; D008253:Macaca mulatta; D018449:SAIDS Vaccines; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination
D000956:Antigens, Viral; D018449:SAIDS Vaccines