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HIV-1 Fusion Peptide-directed Vaccine Design Using Virus-like Particles

Award Number: R01AI162267
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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HIV-1 Fusion Peptide-directed Vaccine Design Using Virus-like Particles - PROJECT SUMMARY There is an unmet need in the HIV vaccine field for immunogens that consistently elicit potent serum antibodies that neutralize a broad spectrum of HIV-1 variants in circulation worldwide. Recently, we identified a novel target for human neutralizing antibodies (NAbs): the eight N-terminal amino acids of the fusion peptide (FP) on prefusion HIV-1 envelope (Env) trimer (Science 2016). We then created a novel immunization strategy: priming with FP conjugated to the carrier protein keyhole limpet hemocyanin (FP-KLH) and boosting with HIV-1 Env trimer. This strategy has reproducibly elicited FP-directed cross-reactive NAbs in multiple studies involving mice, guinea pigs and non-human primates (NHPs), although not in every animal (Nat Med 2018, Cell 2019). The best monoclonal antibody (mAb) from an immunized NHP neutralized 98% of 58 wild-type HIV-1 strains with FP sequence matching the immunogen, and 59% of 208 strains that represent viruses worldwide and contain diverse FP sequences. Therefore, FP prime/Env boost is a promising strategy for eliciting NAb responses. To further improve FP-directed vaccine design, two main limitations need to be addressed. First, the neutralization breadth of the polyclonal sera from immunized animal is still limited. Second, the cross-neutralizing activities were only observed in a small subset of immunized animals and were generally low-titer. To address these limitations, in this proposal, we will develop novel FP immunogens and immunization strategies to improve the breadth (Aim 1), magnitude (Aim 2) and quality (Aim 3) of the FP-directed responses in guinea pigs and non- human primates.


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: 2026 ( Subtotal = $0 )
2026	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	12/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $879,691 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	2/12/2025	NON-COMPETING CONTINUATION	$879,691
														Subtotal = $879,691

Issue Date FY: 2024 ( Subtotal = $1,059,998 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	2/6/2024	NON-COMPETING CONTINUATION	$818,998
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	4	7/23/2024	SUPPLEMENT FOR EXPANSION	$150,000
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	4	5/23/2024	NON-COMPETING CONTINUATION	$91,000
														Subtotal = $1,059,998

Issue Date FY: 2023 ( Subtotal = $1,054,497 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	1/19/2023	NON-COMPETING CONTINUATION	$909,998
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	3	8/18/2023	NON-COMPETING CONTINUATION	$144,499
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	3	4/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,054,497

Issue Date FY: 2022 ( Subtotal = $907,275 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	2/16/2022	NON-COMPETING CONTINUATION	$907,275
														Subtotal = $907,275

Issue Date FY: 2021 ( Subtotal = $923,921 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	3/1/2021	NEW	$923,921
														Subtotal = $923,921

Grand Total All Awards = $4,825,382

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HIV-1 Fusion Peptide-directed Vaccine Design Using Virus-like Particles

Award Number: R01AI162267

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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