# MVA Prime/Novel Trimeric Cyclically Permuted Envelope Protein Boost Vaccines for HIV

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $766,724

## Abstract

The overall goal of this application is to determine the immunogenicity and protective efficacy of novel trimeric
gp120 immunogens against HIV using the rhesus macaque model. Development of an effective vaccine
against HIV-1 has been an elusive goal for the past three decades. The results from the RV144 efficacy trial in
Thailand provided a first proof in humans that HIV infection can be prevented by vaccination and demonstrated
that anti-envelope (Env) antibody response contributes significantly for this protection. The major correlate of
protection was found to be non-neutralizing antibodies specific for the variable loops V1V2 of gp120, a finding
supported by recent non-human primate (NHP) trials in which protection from neutralization resistant simian
immunodeficiency virus (SIV) infection also correlated with anti-V1V2 antibodies. Thus, we hypothesize HIV
vaccines that generate a strong and broad anti-V1V2 response, in addition to neutralizing antibody response,
will significantly improve protection against diverse HIV-1 isolates. Towards this, we recently described the
design, immunogenicity and efficacy of a novel trimeric gp120 immunogen, CycP-gp120. This immunogen is
based on a cyclically permuted gp120 in which a de novo N-terminus is generated within the V1 loop region
with the native N- and C- termini joined via an amino acid linker chain. To induce a trimeric complex, the
human cartilage matrix protein (hCMP) coiled-coil trimerization domain was fused to the de novo N-termini,
resulting in a stabilized, disulfide bond linked trimeric gp120. Immunization of guinea pigs with cycP-gp120
showed strong induction of neutralizing antibodies against neutralization resistant (tier-2) HIV-1 isolates from
multiple clades. Immunization of rabbits and rhesus macaques showed induction of high levels of high avidity
HIV-1 Env specific antibodies with a remarkable anti-gp70-V1V2 specific response, promoting antibodies
recognizing V1V2 sequences from a diverse, multi-clade panel of global HIV-1 isolates. More recent studies in
rhesus macaque showed that MVA prime/CycP boost regimen confers protection against pathogenic SHIV
challenges. In this proposal we will further optimize the CycP immunogen design and the adjuvant for CycP
protein boost, and test the ability of CycP-induced antibody response to further enhance protection against HIV
using a heterologous pathogenic tier 2 SHIV challenge in rhesus macaques.

## Key facts

- **NIH application ID:** 10219067
- **Project number:** 5R01AI148378-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao Amara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $766,724
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219067

## Citation

> US National Institutes of Health, RePORTER application 10219067, MVA Prime/Novel Trimeric Cyclically Permuted Envelope Protein Boost Vaccines for HIV (5R01AI148378-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219067. Licensed CC0.

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