AEGiS-15IAC: Cross-subtype cellular and humoral responses in rhesus monkeys following multiprotein HIV-1 (CRF02

AEGiS-15IAC: Cross-subtype cellular and humoral responses in rhesus monkeys following multiprotein HIV-1 (CRF02_AG) DNA/MVA vaccination.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Cross-subtype cellular and humoral responses in rhesus monkeys following multiprotein HIV-1 (CRF02_AG) DNA/MVA vaccination.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1346)

Ellenberger D, Wyatt L, Li B, Buge S, Lanier N, Rodriguez I, Sariol C, Martinez M, Smith J, Otten R, Kraiselburd E, Moss B, Robinson H, McNicholl J, Butera S
Centers for Disease Control and Prevention, Atlanta, GA, United States

BACKGROUND: Because of the broad spectrum of HIV-1 subtypes circulating in West and West-Central Africa, we evaluated the cross-subtype responses to our vaccine based on the CRF02_AG recombinant subtype. The vaccine consists of priming with plasmid DNA and boosting with recombinant modified vaccinia Ankara (rMVA) both encoding Gag-Pol-Env of an HIV-1 AG primary isolate from Ivory Coast.

METHODS: At 0, 8, and 26 weeks, sixteen young adult rhesus macaques were primed with DNA plasmids encoding for either mature or non-mature virus-like particles (VLPs) and followed at 41 weeks with a rMVA booster. We evaluated the extent of the cellular cross-recognition for diverse HIV-1 subtypes by using Gag and Env peptide pools from Kenyan A, U. S. B, and Thai AE sequences.

RESULTS: The DNA vaccine constructs primed significant cross-subtype CTL responses, and the mature VLP-priming raised two-fold higher cumulative ELISPOTs against Gag epitopes (autologous and cross-subtype). Excellent Gag reactivity within subytpe A, AE recombinant, and B viruses was observed. On average, 14 vaccinated animals responded well to Kenyan A, Thai AE and U. S. B Gag peptide pools. Less cross-reactivity was observed with Env peptide pools; but good Env reactivity was observed within subytpe A and AE recombinant viruses. Despite an overall reduction (15.1%) in cumulative ELISPOTs from peak to memory, ENV reactivity increased by 218%, suggesting a shift in epitope recognition. Western blot analysis demonstrated significant reactivity to AG proteins and cross-subtype western blots are currently being evaluated.

CONCLUSIONS: The observed cross-reactive responses may suggest that this multiprotein DNA/MVA vaccine will successfully translate into significant recognition of recombinant HIV-1 or cross-protection in diverse regions of West Africa and beyond.

Keywords: AEGIS, HIV-1, Genes, gag, Genes, env, Macaca mulatta, Genes, pol, Vaccination, Africa, Central, Vaccines, DNA, HIV-1 Reverse Transcriptase, Africa, Cote d'Ivoire, Animal, Adult, genetics, immunology

040711
ThOrA1346