AEGiS-15IAC: Lack of protection from HIV-1 infection by a HLA-B27-restricted anti-p24 Gag CD8+ T cell response induced by a recombinant HIV canarypox vaccine vector (vCP205).

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Lack of protection from HIV-1 infection by a HLA-B27-restricted anti-p24 Gag CD8+ T cell response induced by a recombinant HIV canarypox vaccine vector (vCP205).

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1394)

Ferrari G, Betts MR, Exley B, Teaberry V, Price DA, Tomaras G, Douek D, Roederer M, Koup RA, Weinhold K, Goepfert P
Vaccine Research Center/NIH, Bethesda, United States

BACKGROUND: We examined the HLA-B27 restricted anti-p24 263-272 (KK10) CD8+ T cell response induced by a HIV recombinant canarypox vaccine (vCP205, AVEG trial 202) in a vaccine recipient who became HIV infected two years post immunization (HOPO).

METHODS: The anti-KK10 response in HOPO was compared to those detected in three HIV-infected HLA-B27+ individuals, one of whom (FRRA) controlled and two (PHTI, D08) who failed to control viremia. Ten-color flow cytometry was used to characterize the function and phenotype of the anti-KK10 CD8+ T cells. In addition, we sequenced the TCRBV CDR3 region of the anti-KK10 CD8 T cells.

RESULTS: Following immunization 0.14% functional CD8+B27-KK10 tetramer+ cells were detectable in HOPO. These cells exhibited both central and memory effector phenotypes as determined by CD27, CD28, CD45RO, CD45RA, CCR7, and CD57 staining. Approximately 6 weeks after infection, the KK10 CD8+ T cell response in HOPO expanded to 5.8% of total CD8+ T cells, and shifted to an effector memory phenotype (CD45RO+CD57+CD27-CD28-), similar to that observed in PHTI and D08. In contrast, FRRA exhibited a diverse memory phenotype (CD45RO+CD57±CD27[dull/bright]CD28-). Only 40% of the CD8+ KK10 tet+ cells in HOPO responded to the KK10 epitope (CD107a+IFNg+TNFa±IL2±). Similar percentages and cytokine pattern were also observed in PHTI and D08, with the exception of IL2 production. In contrast, 80% of the CD8+B27-KK10 tet+ cells responded in FRRA being CD107a+IFNg+TNFa/-IL2-. The KK10 tet+ cells in FRRA and PHTI were essentially monoclonal in nature, while an oligoclonal expansion was observed in HOPO. Conclusion Despite the presence of HIV-specific CD8+ T cells prior to infection, HOPO became infected and was unable to control HIV viremia. These results indicate that preexisting HIV-specific CD8+ CTL recognizing a single immunodominant epitope are alone not sufficient to protect from infection or subsequent disease progression.

Keywords: AEGIS, HIV, HIV Infections, HIV Seropositivity, Acquired Immunodeficiency Syndrome, Antigens, CD8, Genes, gag, CD8-Positive T-Lymphocytes, HLA-B27 Antigen, Antigens, CD28, Antigens, CD45, Antigens, CD27, Antibodies, Disease Progression, HIV Antigens, Antigens, CD, HIV Seronegativity, Thomsen-Friedenreich antibodies, lysosome-associated membrane glycoproteins, immunology, genetics

040711
ThOrA1394