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Population genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding colonies

Award Number: R24AI162317
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Population genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding colonies - PROJECT SUMMARY A strategic priority for contemporary HIV vaccine research is the development of approaches to elicit broadly neutralizing antibodies (bNAbs) able to neutralize diverse strains of the virus. A cornerstone of bNAb discovery is the ability to conduct accurate, longitudinal studies of antibody evolution in HIV infected individual as they gain mutations and acquire neutralization activity. Currently, it is not possible to perform analogous antibody evolution tracing studies using rhesus macaques (RMs), due to a lack of defined immunoglobulin (IG) alleles. This is best exemplified by a recent study large scale vaccine study by our group in which we sequenced a de novo genome of a RM using long-read sequencing in order to obtain accurate assemblies of the IG loci. This reference significantly enhanced the accuracy of tracking the mutations from germline elicited by our vaccine strategies. This tool was critical in deciphering trajectories that led to either autologous neutralization or immunodominance and non-neutralizing responses. In other work, we have developed novel bioinformatics methodology (germline inference) to identify the unmutated germline antibody sequence from immunoglobulin repertoire. This work has led to identification of hundreds of novel inferred IG alleles. The goal of this R24 proposal is to build on these findings by characterizing the IG alleles and haplotypes in AIDS designated RMs at NHP primate centers that serve the major HIV vaccine stakeholders. Currently, the IG loci are poorly characterized in RMs, in part due to technical challenges. IG genotypes are not currently used as criteria when enrolling RMs into vaccine studies. In contrast, MHC genotyping of RMs has become standard practice for vaccine studies and is a core function in genetic management of NPRC RM colonies. The lack of genetic data on the RM IG loci is therefore a significant knowledge gap and impairs our ability to assess the evolution of antibodies in monkeys administered vaccines that aim to elicit neutralizing antibodies. The goal of this R24 proposal is to address this strategic need and build a resource in which this genetic information (IG allele sequence information, haplotype, and allele usage) is available to the HIV vaccine and NHP research communities.


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: 2024 ( Subtotal = $859,777 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	4	4/10/2024	NON-COMPETING CONTINUATION	$859,777
2024	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	3/6/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $859,777

Issue Date FY: 2023 ( Subtotal = $1,267,346 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	3	7/31/2023	SUPPLEMENT FOR EXPANSION	$407,569
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	3/20/2023	NON-COMPETING CONTINUATION	$859,777
														Subtotal = $1,267,346

Issue Date FY: 2022 ( Subtotal = $859,777 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	6/9/2022	NON-COMPETING CONTINUATION	$859,777
														Subtotal = $859,777

Issue Date FY: 2021 ( Subtotal = $790,624 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	4/30/2021	NEW	$790,624
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	1	5/13/2021	NEW	$0
														Subtotal = $790,624

Grand Total All Awards = $3,777,524

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Population genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding colonies

Award Number: R24AI162317

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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