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An early life multivalent immunization strategy for induction of neutralization breadth

Award Number: U01AI192448
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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An early life multivalent immunization strategy for induction of neutralization breadth - ABSTRACT In 2023, adolescents and young people accounted for approximately 25% of new HIV infections globally. The period after weaning but before sexual debut represents a window of relatively low HIV acquisition risk, providing an opportune time for administering a multi-dose vaccine regimen to elicit protective immunity prior to adolescence. The success of a protective HIV vaccine will rely on the induction of broadly neutralizing antibodies (bnAbs). Given the potential for rapid bnAb development in children living with HIV, vaccines targeting B cell evolution towards bnAbs may be more effective in early life. Germline-targeting immunization strategies have shown great potential by using a series of priming, shaping, and polishing immunogens to activate bnAb precursor B cells and guide them towards potent and broad neutralization. While these priming immunogens effectively engage bnAb precursors, identifying appropriate strategies to drive bnAb evolution remains a challenge. The overall goal of this project is to identify an optimal prime-boost strategy to guide antibody maturation towards neutralization breadth in the setting of immune maturation. We hypothesize that an early life HIV immunization strategy incorporating multivalent HIV env immunogens will drive efficient priming and maturation of B cell responses towards neutralization breadth. Our hypothesis will be investigated under the following aims: 1) Compare sequential versus simultaneous administration of germ-line targeting immunogens for induction of CD4bs and V2 apex bnAb precursors; 2) Determine whether a multivalent prime- boost strategy will better drive the development and maturation of bnAb lineages towards neutralization breadth.; and 3) Define the evolution of vaccine-elicited B cell responses and mAbs following immunization with bnAb B cell lineage designed immunogens through a structure-to-sequence approach. The proposed studies will help establish a prime-boost regimen to evolve bnAb B cell lineages throughout early childhood towards neutralization breadth prior to adolescence. These studies will establish early life as an optimal time for beginning a sequential HIV immunization strategy and inform the next phase of bnAb germline-targeting immunization strategies for evaluation in preclinical and human clinical trials.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,275,484 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	8/12/2025	NEW	$1,275,484
														Subtotal = $1,275,484

Grand Total All Awards = $1,275,484

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An early life multivalent immunization strategy for induction of neutralization breadth

Award Number: U01AI192448

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/12/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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