# Vaccine Synergy through Synchronous Delivery

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $741,448

## Abstract

Abstract
As much as 90% of HIV-1 infections occur by transmission at mucosal surfaces. Combating the earliest
events in viral entry is one strategy to combat HIV infection, since it is thought that fewer virions successfully
infect the host at mucosal surfaces. Vaccines that also stimulate the systemic immune system are also
needed to control HIV spread once the mucosal barrier is breached. Systemic immunization by the
intramuscular route can drive mucosal immune responses, but there is also data showing that mucosal
immunization may better educate responses that can act at these first sites of mucosal HIV entry.
We performed vaccine route comparison studies in rhesus macaques that showed that vaginal mucosal
vaccination reduced SHIV-SF162P3 viral loads better than intramuscular immunization. We more recently we
performed an immunogenicity study that compared the effects of vaccine routes using new replicating single-
cycle adenoviruses (SC-Ads) boosted with recombinant gp140 env. Animals immunized by only the
intramuscular route had lower final SHIV neutralizing antibodies in their plasma than animals immunized by
intranasal alone or intranasal and intramuscular vaccinations. Intramuscular animals had high T follicular
helper (Tfh) cells in the blood, but low Tfh in lymph nodes. Conversely, animals immunized by the intranasal
route had high Tfh in lymph nodes, but low Tfh in the blood. Animals immunized by the intramuscular route
had lower antibody-dependent cellular cytotoxicity (ADCC) activities than animals immunized by the mucosal
intranasal route. These data suggest that the route of priming and boosting with gene-based and protein
vaccines may markedly affect the quality and quantity of systemic and mucosal immune responses against
HIV.
In this project, we will build on these interesting vaccine route observations in a team consisting of groups from
Mayo Clinic, MD Anderson, and the Oregon Health & Science University. We will combine our new SC-Ad
vaccines with promising SOSIP protein vaccines and deliver these by a more potent synchronous co-
immunization strategy. We will test how systemic vs. mucosal vaccination drives different systemic and
mucosal immune responses with key analyses of effects on mucosal cell trafficking, Tfh production, and the
production of functional antibodies in systemic and mucosal compartments. We will pursue these efforts in the
following Specific Aims:
Specific Aim 1: Optimize synchronous vaccine strategies that utilize multiple routes of immunizations
to achieve potent systemic and mucosal humoral and cellular responses.
Specific Aim 2: Evaluate the protective efficacy and immune correlates of synchronous systemic and
mucosal vaccination against repeated low dose mucosal challenge by clade C SHIV in rhesus
macaques.

## Key facts

- **NIH application ID:** 9849729
- **Project number:** 5R01AI136718-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Michael A Barry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $741,448
- **Award type:** 5
- **Project period:** 2018-02-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849729

## Citation

> US National Institutes of Health, RePORTER application 9849729, Vaccine Synergy through Synchronous Delivery (5R01AI136718-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849729. Licensed CC0.

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