Experts agree that an effective vaccine against HIV infection will require the induction of potent and broad neutralizing antibody responses. Both the development and clinical evaluation of vaccine candidates requires a sensitive, reproducible and high throughput HIV antibody neutralization assay. Sensitivity and reproducibility are required to confidently measure and assess modest incremental improvements in vaccine design and delivery. High throughput capability is required to accommodate the cost effective and timely evaluation of vaccine candidates in large clinical trials. In addition, a neutralization assay that can be used to evaluate protective immunity in the SIV/macaque model will aid and enable the selection of the most promising candidates for large scale evaluations in human trials. Conventional HIV Antibody Neutralization Assays (i.e. manual PBMC based assays) do not adequately address the current and upcoming demands of heightened HIV vaccine development efforts. In support of these important objectives, Monogram Biosciences (formerly ViroLogic, Inc.) has developed a sensitive neutralizing antibody assay (PhenoSense HIV Antibody Neutralization Assay) that uses viral pseudotypes that express the envelope proteins of patient-derived isolates (see Phase I final report). This assay allows for the direct measurement of autologous neutralizing titers in patient plasma, provides the ability to screen large panels of monoclonal antibodies for neutralizing activity to relevant primary strains, and allows for the direct comparison of antibody responses elicited by different vaccine immunogens. The assay has also been adapted to evaluate SIV envelope proteins and anti-SIV antibody responses in the macaque model. In phase II of this project, we intend to optimize the performance and complete the characterization of the Phenosense HIV Antibody Neutralization Assay. The throughput and capacity of this assay will be augmented using custom automation and other scale-up techniques. The sensitivity, reproducibility and robustness of the assay will be evaluated and compared to the conventional PBMC-based method. We will develop informational database systems focused on linking envelope phenotype and sequence analysis. This database will undoubtedly become a useful tool for vaccine design. Monogram Biosciences intends to commercialize the PhenoSense HIV Antibody Neutralization Assay and associated database systems to support the development and clinical evaluation of new vaccine candidates generated in government, academic, and industrial laboratories.
| van Gils, Marit J; Bunnik, Evelien M; Burger, Judith A et al. (2010) Rapid escape from preserved cross-reactive neutralizing humoral immunity without loss of viral fitness in HIV-1-infected progressors and long-term nonprogressors. J Virol 84:3576-85 |
| van Gils, Marit J; Edo-Matas, Diana; Schweighardt, Becky et al. (2010) High prevalence of neutralizing activity against multiple unrelated human immunodeficiency virus type 1 (HIV-1) subtype B variants in sera from HIV-1 subtype B-infected individuals: evidence for subtype-specific rather than strain-specific neutralizing ac J Gen Virol 91:250-8 |
| van Gils, Marit J; Euler, Zelda; Schweighardt, Becky et al. (2009) Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression. AIDS 23:2405-14 |
