Development of a chimeric syphilis vaccine candidate to combat local, disseminated and congenital syphilis infection

Active Cooperative Agreement Awarded Last action

Award ID
U01AI182035
Recipient
Awarding agency
Obligated
$9,628,753

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 52% complete
Place of performance
2323 Riverside Dr., Ottawa, ON K1H 1A1, Canada

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
In several high-income nations, including the united states, infectious syphilis has been resurgent for over two decades now, while syphilis is still endemic in low- and middle-income countries. Syphilis is therefore still a public global health concern, particularly because IT can lead to neurological sequelae such as dementia and stroke-like syndromes, as well as cardiovascular manifestations potentially leading to death. Furthermore, about half a million pregnancies are adversely affected by congenital transmission of the pathogen every year. The partial success of recent syphilis control campaigns promoted by the CDC and who clearly highlights the necessity of devising novel ways to control this serious infection. The availability of an effective syphilis vaccine could make a significant difference in the global effort to control the spread of this serious infection. Over the last decade, our research programs have had the focus of identifying vaccine candidates among the surface-exposed antigens of the syphilis agent, treponema pallidum subsp. Pallidum (T. Pallidum). These studies have led to the discovery that the T. Pallidum repeat (TPR) protein family and the TP0751 vascular adhesin are critical proteins in the processes of chancre development/immune evasion and systemic dissemination, respectively. When tested in immunization/challenge experiments in the rabbit model of syphilis, these antigens were shown to provide significant protection against infection. Furthermore, within these antigens, we have been able to pinpoint the epitopes necessary to generate a protective host response. To reduce the complexity and production costs of our vaccine candidates, we have developed a chimeric protein platform where the non-functional loops of the TP0751 protein are exchanged with conserved epitopes from the TPR proteins. This approach provides a single construct that retains the critical TP0751 epitopes while allowing presentation of protective epitopes from other antigens in a stable and soluble scaffold. This proposal encompasses the next phase of this research endeavor consisting of investigational new drug (IND)-enabling pre-clinical studies. To this end, we will create future generations of the chimera vaccine candidate to assess the level of induced immunoreactivity and protection, after which the vaccine delivery formulation will be optimized with the lead candidate by performing in vivo immunization/challenge experiments, toxicity and stability tests, and studies investigating compatibility with scale-up production. Collectively these studies are anticipated to provide US with an efficacious syphilis vaccine candidate that is ready for clinical studies.

Transactions

Action Obligated Date
Amendment $0
Amendment $1,594,456
Amendment $1,594,456
Amendment $0
Amendment $0
Amendment $0
Amendment $1,572,419
Amendment $0
Amendment $0
Amendment $1,622,474
Amendment $1,622,474
Original award $1,622,474
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Quick answers

Who received award U01AI182035?

U01AI182035 was awarded to University Of Victoria by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on April 15, 2024.

How much is award U01AI182035 worth?

$9,628,753 has been obligated on U01AI182035.

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