# Subingual-parenteral Vaccination to Prevent Oral HIV Transmission in Infants

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $920,833

## Abstract

ABSTRACT
Every day, about 400 infants acquire HIV-1 globally, the vast majority by breast milk transmission. Late HIV-1
diagnosis in pregnancy, lack of adherence, and acute HIV-1 infection during the breastfeeding period remain
significant hurdles in the prevention of mother-to-child-transmission (MTCT). Thus, to achieve the goal of an
AIDS-free generation, we need preventive measures in addition to antiretroviral therapy (ART). An HIV vaccine
represents a core component of these efforts. Our long-term goal is the development of a pediatric HIV vaccine
to protect against breastmilk transmission of HIV. Despite HIV being transmitted primarily by mucosal routes,
few vaccine strategies explored mucosal routes of immunization to induce protective immune responses at
potential mucosal entry sites, including the oral mucosa in infants. To close these gaps, we started to explore
the potential of oral vaccination in the protection against breastmilk transmission of HIV. Newborn macaques
vaccinated with a combined oral (PO) and intramuscular (IM) DNA-SIV prime and boosted by combined
sublingual (SL) and IM MVA-SIV had a significantly reduced per-exposure-risk of oral SIV infection compared
to infants receiving the same vaccine by the IM route alone. Reduced infection risk was associated with higher
SIV Env gp120 and V1V2 specific IgG antibodies in fecal specimens. Based on this premise, we present the
central hypothesis that a rationally designed combined SL+parental vaccine regimen can prevent oral HIV
acquisition in infants. The rich regional lymphatic network of the Waldeyer’s Ring provides an easy and non-
invasive portal for oral vaccine uptake, and, as an intrinsic part of the systemic lymphatic network, enables the
induction of local and systemic protective immune responses by oral vaccines. The objective of the proposed
studies is to optimize our pediatric vaccine through rational selection of adjuvants and HIV Env immunogens
that can induce Env-specific IgG and IgA antibodies in plasma and at mucosal entry sites, such as the oral
mucosa and the intestine. We will immunize infants by the SL and subcutaneous (SC) route with MVA
expressing SIVgag, pol and the clade C HIV C.1086 envelope (Env) NFL trimer plus Env NFL trimer protein
and test the hypothesis that a combined SL+SC vaccine regimen provides superior efficacy against oral SHIV
CH848 challenge compared to vaccination by only the SC route (Aims 1 and 2). Both Env immunogen and
challenge virus contain Envs of HIV clade C, the clade most prevalent in sub-Saharan Africa where the
majority of pediatric HIV infections occur, emphasizing the clinical relevance of our studies. We further test
novel adjuvants that were selected to specifically enhance mucosal immune responses and the priming
function of infant dendritic cells. To identify pathways that are essential for the generation of highly functional
antibody responses in infants and are associated with protection against oral SHIV CH848 challen...

## Key facts

- **NIH application ID:** 10172886
- **Project number:** 5R01DE028146-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kristina De Paris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $920,833
- **Award type:** 5
- **Project period:** 2018-09-06 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172886

## Citation

> US National Institutes of Health, RePORTER application 10172886, Subingual-parenteral Vaccination to Prevent Oral HIV Transmission in Infants (5R01DE028146-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10172886. Licensed CC0.

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