Retrospective Proteomic Analysis of Cellular Immune Responses and Protective Correlates of p24 Vaccination in an HIV Elite Controller Using Antibody Arrays.
HIV p24 is an extracellular HIV antigen involved in viral replication. Falling p24 antibody responses are associated with clinical disease progression and their preservation with non-progressive disease. Stimulation of p24 antibody production by immunization to delay progression was the basis of discontinued p24 vaccine. We studied a therapy-naive HIV+ man from Sydney, Australia, infected in 1988. He received the HIV-p24-virus like particle (VLP) vaccine in 1993, and continues to show vigorous p24 antigen responses (>4% p24-specific CD4⁺ T cells), coupled with undetectable plasma viremia. We defined immune-protective correlates of p24 vaccination at the proteomic level through parallel retrospective analysis of cellular immune responses to p24 antigen in CD4⁺ and CD8⁺ T cells and CD14⁺ monocytes at viremic and aviremic phases using antibody-array. We found statistically significant coordinated up-regulation by all three cell-types with high fold-changes in fractalkine, ITAC, IGFBP-2, and MIP-1α in the aviremic phase. TECK and TRAIL-R4 were down-regulated in the viremic phase and up-regulated in the aviremic phase. The up-regulation of fractalkine in all three cell-types coincided with protective effect, whereas the dysfunction in anti-apoptotic chemokines with the loss of immune function. This study highlights the fact that induction of HIV-1-specific helper cells together with coordinated cellular immune response (p < 0.001) might be important in immunotherapeutic interventions and HIV vaccine development.
Department of Medicine, University of Sydney, Sydney 2000, Australia. perera.suneth@gmail.com.
Suneth S
SS
Perera
Department of Medicine, University of Sydney, Sydney 2000, Australia. bin.wang1@unsw.edu.au.
Bin
B
Wang
Department of Cytogenetics, Children's Hospital at Westmead, Sydney 2000, Australia. Arturo.damian@health.nsw.gov.au.
Arturo
A
Damian
Australian Red Cross Blood Service, 17 O'Riordan Street, Alexandria NSW 2015 and School of Medical Sciences, (Faculty of Medicine) University of Sydney, Sydney 2000, Australia. Wayne.dyer@sydney.edu.au.
Wayne
W
Dyer
Department of Medicine, University of Sydney, Sydney 2000, Australia. li.zhou@health.nsw.gov.au.
Li
L
Zhou
Department of Medicine, University of Sydney, Sydney 2000, Australia. vickanc@hotmail.com.
Viviane
V
Conceicao
Department of Medicine, University of Sydney, Sydney 2000, Australia. nitin.saksena@sydney.edu.au.
Nitin K
NK
Saksena
Acquired immune deficiency syndrome (AIDS); Antibody microarray; CD4+ T; CD8+ T cells; HIV; chemokines; cytokines; immune responses; monocyte; p24 vaccine