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Design and Use of HIV-1 Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibody Responses David C. Montefiori, Ph.D. Laboratory for AIDS Vaccine Research & Development Duke University Medical Center Durham, NC firstname.lastname@example.org
Design and Use of HIV-1 Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibody Responses
David C. Montefiori, Ph.D.
Laboratory for AIDS Vaccine Research & Development
Duke University Medical Center
HIV-1 exhibits an extraordinary degree of genetic variability that has given rise to multiple genetic subtypes and circulating recombinant forms (CRFs) of the virus. Information on the neutralization properties of each major genetic subtype and CRFs will inform vaccine design and will facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.
The choice of target viruses has a significant influence on the outcome and interpretation of assay results
SPECTRUM OF NEUTRALIZATION-SENSITIVITIES
TCLA & some 1o isolates
Desired reference strains
Where most vaccine-elicited responses are now
V3 & CD4i sensitive
strains not included in the vaccine.
Panel of heterologous viruses matching the
genetic subtype(s) of the vaccine; 12 viruses per panel.
May include additional strains from vaccine trial sites
Multi-clade panel comprised of six tier 2 viruses of each
genetic subtype, excluding the genetic subtype(s) evaluated in Tier 2.
May include additional strains from the proposed vaccine trial site.
J. Virol. 79:10103-10107 (2005)
Multi-Tiered Approach to Assessing Vaccine-Elicited NAb Responses
J. Virol. 79:10108-10125 (2005) – Clade B panel
J. Virol., in press (2006) – Clade C panel
These parameters are only part of a decision pathway that includes other immune responses.
Mascola, J. R., P. D'Souza, P. Gilbert, B. Hahn, N. L. Haigwood, L. Morris, C. J. Petropoulos, V. R. Polonis, M. Sarzotti-Kelsoe, and D. C. Montefiori. 2005. Recommendations for the design and use of standard virus panels to assess the neutralizing antibody response elicited by candidate human immunodeficiency virus type 1 vaccines. J. Virol. 79:10103-10107.
CLADE B REFERENCE PANEL:
Li, M., F. Gao, J.R. Mascola, L. Stamatatos, V.R. Polonis, M. Koutsoukos, G. Voss, P. Goepfert, P. Gilbert, K.M. Greene, M. Bilska, D.L. Kothe, J.F. Salazar-Gonzalez, X. Wei, J.M. Decker, B.H. Hahn, and D.C. Montefiori. 2005. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol., 79:10108-10125.
CLADE C REFERENCE PANEL:
Li, M,. J.F. Salazar-Gonzalez, C.A. Derdeyn, L. Morris, C. Williamson, J.E. Robinson, J.M. Decker, Y. Li, M.G. Salazar,V.R. Polonis, K. Mlisana, S.A. Karim, K. Hong, K.M. Greene, M. Bilska, J.T. Zhou, S. Allen, E. Chomba, J. Mulenga, C. Vwalika, F. Gao, M. Zhang, B.T.M. Korber, E. Hunter, B.H. Hahn, and D.C. Montefiori. 2006. Genetic and neutralization properties of acute and early subtype C human immunodeficiency virus type 1 molecular env clones from heterosexually acquired infections in southern Africa. J. Virol., in press.
Brown, B. K., J. M. Darden, S. Tovanabutra, T. Oblander, J. Frost, E. Sanders-Buell, M. S. DeSouza, D. L. Birx, F. E. McCutchan, and V. R. Polonis. 2005. Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 (HIV-1) isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines. J. Virol. 79:6089-6101.