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Development of a Safe and Potent Vaccine Against Melioidosis using the LVS dcapB Vector Platform

Award Number: R01AI141390
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Burkholderia pseudomallei (Bp), an environmental bacterium capable of infecting humans and animal hosts, is the causative agent of melioidosis, a highly fatal disease endemic in many tropical areas. In addition to its significant public health burden in endemic regions, causing ~89,000 deaths annually, Bp is categorized as a Tier 1 Select Agent of bioterrorism, in large part because inhalation of low doses of Bp can cause rapidly fatal pneumonia. As naturally acquired melioidosis is often difficult to diagnose and requires very lengthy treatment, and as post-exposure prophylaxis is not a practical public health policy for countering an outbreak of pneumonic melioidosis from a bioterrorist attack, a safe and effective pre-exposure vaccine would be highly beneficial in both circumstances. Currently, there are no licensed vaccines against Bp. Hence, a vaccine against Bp would be of great benefit to people living in endemic regions, travelers, and military personnel stationed in these areas, and it would also reduce the risk from an intentional release in a bioterrorist attack. The goal of this application is to develop a safe and highly potent vaccine against Bp, suitable for both biodefense and public health purposes, based on a readily expandable single vector platform vaccine. Specifically, we shall use a novel, safe, yet potent live attenuated vector, LVS ¿capB. The LVS ¿capB vector, developed in this laboratory, is a further attenuated version (>10,000 fold less virulent in mice) of a multi- deletional Francisella tularensis vaccine (F. tularensis subsp. holarctica Live Vaccine Strain; LVS) already extensively tested in humans; hence, LVS ¿capB is anticipated to be exceedingly safe. Moreover, recombinant vaccines comprising this vector have been shown to induce potent humoral and cell-mediated (including both CD4+ and CD8+) immune responses, all likely important to long-lasting potent immunoprotection against Bp. In preliminary studies, homologous boosting with rLVS ¿capB vaccines expressing immunoprotective Bp antigens has already demonstrated impressive protective efficacy against respiratory challenge with virulent Bp in sensitive BALB/c mice; protection was superior to the unlicensed attenuated Bp82 vaccine, which is unlikely to be approved because of concerns about reversion to virulence and the possibility of causing chronic disease. To accomplish our goal of developing a safe and highly potent vaccine against Bp, we shall a) construct optimized rLVS ¿capB vaccines expressing multiple immunoprotective Bp antigens as fusion proteins; b) evaluate the vaccines systematically in vitro for protein expression, growth kinetics, and stability; c) evaluate the vaccines administered by different routes for safety, dissemination, clearance, and stability in both immune competent and immune deficient mice; d) evaluate protective efficacy against challenge with highly virulent Bp by the respiratory (IN) route, the route of greatest concern in a bioterrorist attack, and by the subcutaneous route, the route principally responsible for natural infection; and e) explore correlates of protective immunity using vaccines of escalating efficacy.


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: 2023 ( Subtotal = $775,813 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	5	5/31/2023	SUPPLEMENT FOR EXPANSION	$155,111
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	5/26/2023	NON-COMPETING CONTINUATION	$620,702
														Subtotal = $775,813

Issue Date FY: 2022 ( Subtotal = $775,812 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	4	6/13/2022	SUPPLEMENT FOR EXPANSION	$155,110
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	4	6/10/2022	NON-COMPETING CONTINUATION	$620,702
														Subtotal = $775,812

Issue Date FY: 2021 ( Subtotal = $775,812 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	002	3	5/19/2021	NON-COMPETING CONTINUATION	$775,812
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	2	12/31/2020	SUPPLEMENT FOR EXPANSION	$155,110
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	12/31/2020	NON-COMPETING CONTINUATION	-$155,110
														Subtotal = $775,812

Issue Date FY: 2020 ( Subtotal = $775,812 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	5/5/2020	NON-COMPETING CONTINUATION	$775,812
														Subtotal = $775,812

Issue Date FY: 2019 ( Subtotal = $789,812 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	5/29/2019	NEW	$789,812
														Subtotal = $789,812

Grand Total All Awards = $3,893,061

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Development of a Safe and Potent Vaccine Against Melioidosis using the LVS dcapB Vector Platform

Award Number: R01AI141390

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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