# Approaches to Improve the Efficacy of Prime-boost Immunization against HIV/AIDS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $891,161

## Abstract

PROJECT SUMMARY/ABSTRACT
To date, the only vaccine trial (RV144) that has shown any protective efficacy against HIV acquisition is based
on a poxvirus prime – protein boost immunization strategy. Although the efficacy achieved was modest
(~31%), these findings provide a strong rationale to seek improvements for the prime-boost immunization
approach and to gain better insight on the nature of the protective immunity achieved. Correlate studies of the
RV144 trial indicated that antibodies against the hypervariable loops 1 and 2 (V1/V2) region of HIV envelope
protein (Env) and high levels of antibody-dependent cellular cytotoxicity (ADCC) activities inversely correlated
with the risk of HIV-1 acquisition. Neutralizing antibodies (Nabs) were generated, but were primarily against
sensitive (“Tier 1”) isolates, with little or no activity against the more resistant (“Tier 2”) strains typical of
circulating viruses. Thus, much of the current effort in HIV vaccine research aims to elicit Tier 2 Nabs and to
improve the potency and the breadth of non-neutralizing antibody responses, including V1/V2 directed
antibodies and antibodies that can mediate ADCC. Using a replication-competent poxvirus for priming and
gp120 for boosting, we were able to induce Nab against heterologous Tier 2 viruses as well as cross-reactive
V1/V2-specific antibodies and high levels of ADCC activities in rabbits. In this application, we propose to
examine novel immunogens and immunization approaches to further enhance the breadth and potency of the
Nab and non-Nab responses achieved and to determine if findings in rabbits can be translated to non-human
primates. We hypothesize that by presenting the Env antigen in a native trimer form with the conserved CD4
binding site unmasked, we will enhance cross-reactive Nab, and by using polyvalent Env immunogens, we will
amplify responses to conserved epitopes, while broadening strain-specific responses, including those directed
to variable regions. The enhanced breadth and potency of both Nab and non-Nab responses, including V1/V2-
directed antibodies and those that mediate antiviral effector functions, such as ADCC, will contribute to
protection against challenge in a non-human primate model. The Specific Aims are: (1) To determine if trimeric
Env, instead of monomeric gp120, when used as the boosting immunogen in a prime-boost regimen may
improve the breadth or potency of Nab responses; (2) To determine if the ability of a highly conserved glycan
(N197) to modulate Env immunogenicity is dependent on the use of trimeric Env, instead of monomeric gp120;
(3) To determine if polyvalent, rather than monovalent Env, when used in a prime-boost immunization regimen,
can improve the breadth and potency of Env-specific antibody responses; and (4) To examine if immunization
regimens down-selected from the preceding studies in rabbits can be translated to macaques and if the
immune responses generated can protect against SHIV challenge. If successful...

## Key facts

- **NIH application ID:** 9844923
- **Project number:** 5R01AI129673-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Shiu-Lok Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $891,161
- **Award type:** 5
- **Project period:** 2017-02-06 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844923

## Citation

> US National Institutes of Health, RePORTER application 9844923, Approaches to Improve the Efficacy of Prime-boost Immunization against HIV/AIDS (5R01AI129673-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844923. Licensed CC0.

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