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Nucleic acid-based formulation of cytomegalovirus-vectored HIV vaccines

Award Number: R41AI150232
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: 04/07/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2021

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Nucleic acid-based formulation of cytomegalovirus-vectored HIV vaccines - This grant is for translational development of a scalable, nucleic acid-based formulation of cytomegalovirus-vectored vaccines that can be distributed without a cold chain. HIV candidate vaccines that use cytomegalovirus (CMV) as delivery vector and immunomodulatory adjuvant have shown extraordinary promise. In our preliminary work, for example, a rhesus cytomegalovirus-vectored SIV vaccine lacking the viral IL-10 gene (RhCMVdIL10-SIVgag) protected 4/6 infants from SIV infection. Tendel Therapies Inc. is licensing a portfolio of technology centered on these second-generation, CMV-vectored vaccines. Manufacturing and distribution of CMV-based vaccines present daunting challenges: (i) replication of CMV in culture is markedly slower than that of other vaccine vectors; (ii) CMV undergoes rapid genetic change when amplified in culture; (iii) the virus is enveloped and thus difficult to separate from cell- and virus-derived lipid bilayers of a similar size; (iv) methods for extreme concentration of the heterogenous particles are unknown; and (v) a cold chain is required for distribution. To eliminate these problems, Tendel is also licensing technology for vaccine delivery using purified CMV genomes propagated in E. coli. The technology permits efficient “rescue” of the genomes after introduction to mammalian cells. Similarly efficient rescue in vivo should lead to immune responses that are equivalent to those provoked by conventional vaccination with virions. We hypothesize that viral IL-10-deficient, CMV-vectored vaccine genomes (DNA) provoke immune responses that are indistinguishable from the protective responses stimulated by encapsidated live vaccine. Aim 1. Assess antigen expression and vaccine vector replication after delivery of vaccine genomes to macaques. CMV-vectored vaccines given as virions first replicate locally, leading to inflammatory cell influx, and then systemically, leading to viral gene expression in distant tissues. Our hypothesis predicts that successful rescue of vaccine genomes should lead to the same events. Aim 2. Test if innate and adaptive immune responses to vaccination with nucleic acid are comparable to protective anti-SIV responses observed previously. Previous studies have shown that protection against SIV is associated with specific immune responses, particularly Mamu-E-restricted CD8+ T cell responses. These innovative Phase I experiments will be sufficient to establish both the technical merit and—in light of the proven commercial interest in CMV-vectored vaccines—the commercial potential of Tendel's approach. Phase II experiments will build on this work to (i) demonstrate that macaques vaccinated with nucleic acid are protected against SIV challenge (ii) continue development of replication-defective HCMV-HIV Gag and Env vaccines.


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: 2022 ( Subtotal = $0 )
2022	2020	TENDEL THERAPIES INC	420 YALE AVE	KENSINGTON	CA	94708	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	1	5/20/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $300,000 )
2020	2020	TENDEL THERAPIES INC.	420 YALE AVE	KENSINGTON	CA	94708	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	1	4/6/2020	NEW	$300,000
														Subtotal = $300,000

Grand Total All Awards = $300,000

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Nucleic acid-based formulation of cytomegalovirus-vectored HIV vaccines

Award Number: R41AI150232

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: 04/07/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2021

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