Structure-Based Vaccine Design against HIV-1

Identifying HIV vaccine candidates to achieve protection against regional HIV strains circulating in a localized population

The Problem
Despite the implementation of multiple sound prevention strategies and the advent of effective medication regimens for controlling HIV, virus transmission continues to be a major public health challenge throughout the world.
The Solution
Researchers evaluated the shared structural characteristics of HIV envelope proteins to design vaccine candidates with the potential for protecting against diverse HIV strains.

Overview

The development of a safe and effective vaccine against HIV/AIDS has been elusive yet remains the best hope for ending the HIV/AIDS epidemic in countries with limited health care resources. One promising approach involves developing vaccines to elicit immune responses resulting in the production of antibodies that neutralize the activity of the HIV-1 trimeric envelope spike protein (Env), which mediates virus entry into cells. This approach has been hampered by the incredible diversity of HIV strains that circulate in populations around the world. Vaccine candidates that induce antibodies that can neutralize one strain of HIV have so far been unable to block most other circulating strains, resulting in protection that is too narrow to be useful. The challenge has been finding a vaccine candidate able to induce antibody responses that can neutralize a broad variety of HIV strains.

This project attempted to narrow the scope of the challenge by collaborating with an ongoing longitudinal study (funded separately by Grand Challenges China) that monitors a high-risk population in China to discover the limited number of HIV-1 stains circulating within the localized population. The researchers evaluated the structures of Env proteins from individuals newly infected with HIV-1 to assess shared characteristics having the potential to elicit protective immunity. Using this information, the researchers designed novel Env proteins, engineering them into a vector-based delivery system, and set out to evaluate the vaccine candidates in small-animal and non-human primate models.

Launched in April 2017, the project concluded in September 2021.

Partners

*Provided financial support

FNIH Contacts

David Brown, Scientific Program Manager, dbrown@fnih.org
Rebeca Salmeron, Project Manager, rsalmeron@fnih.org

Goals

  • Use a structure-based approach to design envelope immunogens derived from the most dominant HIV-1 strains transmitted among a high-risk population in a localized community
  • Evaluate the ability of rationally designed Env immunogens to elicit broadly neutralizing antibodies in small animals and non-human primate models.

Results and Accomplishments

This project made significant technical advances in HIV Env design, production, and purification that are sure to impact the HIV vaccine field moving forward. Moreover, the researchers designed several promising stable Env trimeric proteins that can be produced efficiently for evaluation as vaccine candidates in animal models. Future experiments will help the researchers gain a better understanding of the immune responses the vaccine candidates elicit, as well as their potential for providing vaccine-induced protection.