Preclinical Evaluation Of Neutralizing Antibodies Elicited by HIV-1 Immunogens

Mascola, John R.

Abstract

The present studies examine the breadth and magnitude of neutralizing antibody (NAb) responses in small animals and rhesus monkeys after various immunization regimens. Using a standardized multi-tier panel of reference Env pseudoviruses for NAb assessment, we show that both protein immunization, and DNA prime, rAd boost immunization, can generate high antibody titers. The potency and breadth of neutralization of primary viruses is still limited. Ongoing optimization of immunogen design will lead to new vaccines to test.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI005012-07
• Application #: 7732735
• Support Year: 7
• Fiscal Year: 2008
• Total Cost: $320,240

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Wu, Lan; Zhou, Tongqing; Yang, Zhi-yong et al. (2009) Enhanced exposure of the CD4-binding site to neutralizing antibodies by structural design of a membrane-anchored human immunodeficiency virus type 1 gp120 domain. J Virol 83:5077-86

Morner, Andreas; Douagi, Iyadh; Forsell, Mattias N E et al. (2009) Human immunodeficiency virus type 1 env trimer immunization of macaques and impact of priming with viral vector or stabilized core protein. J Virol 83:540-51

Phogat, S; Svehla, K; Tang, M et al. (2008) Analysis of the human immunodeficiency virus type 1 gp41 membrane proximal external region arrayed on hepatitis B surface antigen particles. Virology 373:72-84

Montefiori, David; Sattentau, Quentin; Flores, Jorge et al. (2007) Antibody-based HIV-1 vaccines: recent developments and future directions. PLoS Med 4:e348

Dey, Barna; Pancera, Marie; Svehla, Krisha et al. (2007) Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. J Virol 81:5579-93

Shu, Yuuei; Winfrey, Sarah; Yang, Zhi-Yong et al. (2007) Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs. Vaccine 25:1398-408

Seaman, Michael S; Leblanc, Daniel F; Grandpre, Lauren E et al. (2007) Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens. Virology 367:175-86

Wang, Shixia; Pal, Ranajit; Mascola, John R et al. (2006) Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E. Virology 350:34-47

Rao, Srinivas S; Gomez, Phillip; Mascola, John R et al. (2006) Comparative evaluation of three different intramuscular delivery methods for DNA immunization in a nonhuman primate animal model. Vaccine 24:367-73

Wu, Lan; Yang, Zhi-Yong; Xu, Ling et al. (2006) Cross-clade recognition and neutralization by the V3 region from clade C human immunodeficiency virus-1 envelope. Vaccine 24:4995-5002