8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 28)

M. W. Cho¹, Y. B. Kim¹, M. K. Lee¹, K. C. Gupta¹, W. Ross¹, R. Plishka¹, A. Buckler-White¹, T. Igarashi¹, T. Theodore¹, R. Byrum², C. Kemp³, D. C. Montefiori⁴, and M. A. Martin^1
1NIH, Bethesda, MD; ²Bioqual, Rockville, MD; ³Kemp Biotechnologies, Frederick, MD; and ⁴Duke Univ., Durham, NC.

BACKGROUND: The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (Nabs) against HIV-1 isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. Most previously evaluated vaccine candidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of Nab and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from either single or multiple viral isolates.

METHODS: Animals were challenged with SHIV DH12 following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (i) LAI, RF, 89.6, AD8 and Bal (Polyvalent); (ii) LAI, RF, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6); and (iv) DH12 (Monovalent-DH12).

RESULTS: Animals in the two polyvalent vaccine groups developed Nabs against more HIV-1 isolates compared to those in the two monovalent vaccine groups (p=0.0054). However, the increased breadth was directed almost entirely against the vaccine strains. Resistance to SHIV_DH12strongly correlated with the level of Nabs directed against the virus on the day of challenge (p=0.0008). Accordingly, the animals in the Monovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to the SHIV_DH12challenge than the macaques immunized with preparations lacking a DH12 component (viz Polyvalent and Monovalent-89.6) (p=0.039).

CONCLUSIONS: Despite the absence of any detectable Nab, animals in Polyvalent vaccine group, but not those immunized with Monovalent-89.6, exhibited markedly lower levels of plasma virus compared to those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.