# VIRUS-LIKE PARTICLES WITH STABILIZED TRIMERIC ENVELOPE FOR PRIME BOOST IMMUNIZATION

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $900,802

## 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. In this application, we seek to improve
responses to prime boost immunization by a combination of three independent approaches: (i) to present
stabilized trimeric Env spikes on virus-like particles (VLP) as immunogens for vaccinia virus prime and VLP
boost; (ii) to incorporate stabilized trimeric envelope (Env) from multiple isolates as polyvalent VLP immunogen
to increase the breadth of response; and (iii) to explore approaches that may increase the number of SOSIP
trimer spikes on VLP. Our overall working hypothesis is that the protective efficacy of prime-boost
immunization can be improved by optimizing immunogen and immunization regimen to enhance the breadth
and potency of both neutralizing and non-neutralizing antibody responses that have been associated with
protection in human and/or non-human primate models. Specifically, we hypothesize that by presenting
stabilized trimeric Env on VLP in the poxvirus-protein prime boost regimen, we will be able to enhance
neutralizing antibody responses, and by using polyvalent Env and increasing the density of Env spikes
on the VLP immunogens, we will further amplify the breadth and the potency of response. The
enhanced breadth and potency of both neutralizing and non-neutralizing antibody responses,
including V1/V2-directed antibodies and those that mediate antiviral effector functions, such as ADCC,
will contribute to the protective efficacy of the poxvirus-protein prime boost immunization platform.
The Specific Aims of this proposal are: (1) To determine the structure and the antigenic and immunogenic
profiles of stabilized Env trimers incorporated into VLP; (2) To determine if stabilized Env trimers from multiple
isolates can be incorporated on VLP and if such polyvalent vaccines when used in a prime/boost regimen will
increase the breadth of Nab and non-Nab responses; (3) To determine if cytoplasmic tail modifications will
increase the density of stabilized Env spikes on VLP and if increased Env density will enhance the breadth and
potency of Env specific responses; and (4) To examine if immunization regimens down-selected from the
preceding studies in rabbits can be translated to macaques. If successful, insights obtained from these studies
will inform the clinical development of vaccines and vaccine strategies that may be more effective than those
used in RV144 to prevent HIV-1 acquisition in humans.

## Key facts

- **NIH application ID:** 9963110
- **Project number:** 5R01AI131403-04
- **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:** $900,802
- **Award type:** 5
- **Project period:** 2017-07-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963110

## Citation

> US National Institutes of Health, RePORTER application 9963110, VIRUS-LIKE PARTICLES WITH STABILIZED TRIMERIC ENVELOPE FOR PRIME BOOST IMMUNIZATION (5R01AI131403-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963110. Licensed CC0.

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