Mechanisms of early-life immunity associated with HIV-1 vaccine-induced neutralizing antibody responses

Active Cooperative Agreement Awarded Last action

Award ID
U01AI192382
Recipient
Awarding agency
Obligated
$2,436,087

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 24% complete
Place of performance
Durham, NC 27710, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
At the end of 2021, an estimated 1.7 million children were living with HIV-1, including 160,000 children who were newly infected (unaids), thus pediatric HIV-1 remains a global health concern. However, there is a GAP in our knowledge of b cell development in early-life that prevents US from implementing the full potential of pediatric HIV-1 vaccines. Understanding the mechanisms of early-life immunity that can establish and maintain vaccine-induced responses to HIV-1 immunogens in pediatric populations will contribute to this knowledge GAP. A primary goal of a prophylactic HIV-1 vaccine is induction of broadly neutralizing antibodies (bnabs) that target the envelope (ENV) surface protein and prevent infection of different circulating HIV-1 strains. Infants and children living with HIV-1 develop HIV-1 ENV-reactive bnabs, and often develop bnabs more rapidly than adults. Young rhesus macaques (RMS) that were simian-HIV (shiv)-infected as infants generated heterologous HIV-1 nabs with bnab characteristics in association with enhanced germinal center (GC) activity, including elevated antigen (AG)-specific GC b cells-a mechanism for bnab induction in humans. Natural killer (NK) cells have also been postulated to act as rheostats regulating GC-dependent anti-viral b cell responses. However, the permissive immunological environment for vaccine-induced HIV-1 ENV-reactive bnab development in early-life are vastly understudied. In this proposal, we will immunize infant RMS with an innovative pediatric vaccine regimen of bnab lineage-inducing HIV-1 ENV immunogens and a clinically- approved hepatitis (HEP) b childhood vaccine known to elicit durable memory b cell responses. We will perform immunologic studies with cells from different b cell compartments (peripheral blood (pbmcs), lymph node (LN), and bone marrow (BM)) in neonatal RMS immunized with the multicomponent cocktail HIV-1 and clinically-approved childhood vaccines in an innovative study design to establish the mechanisms of early-life HIV-1 ENV immunity that elicit nabs, a subset of which has the capacity to develop breadth. The specific aims for this proposal are as follows: aim 1. Define the b cell repertoires elicited by a cocktail pediatric immunization strategy in infant RMS aim 2: define the dynamics and functions of vaccine-induced GC b and t cell subsets in LN, and plasma cells in BM, of infant RMS aim 3. Define the mechanisms of NK cell immunoregulation on the quality of vaccine-induced memory b cells in infant RMS

Transactions

Action Obligated Date
Amendment $1,196,522
Original award $1,239,565

Quick answers

Who received award U01AI192382?

U01AI192382 was awarded to Duke University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 20, 2025.

How much is award U01AI192382 worth?

$2,436,087 has been obligated on U01AI192382.

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