Development of a universal vaccine against leptospirosis
Active Project Grant Awarded Last action
- Award ID
- R01AI182354
- Recipient
-
University Of Connecticut UEI WNTPS995QBM7
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,908,576
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 47% complete
- Place of performance
- Storrs, CT 06269, USA
Award details come from USAspending.gov.
Description
- Abstract
- Leptospirosis, an emerging infectious disease, is a leading zoonotic cause of morbidity and mortality worldwide, conveying the greatest burden to subsistence farmers and urban slum populations. In the US and other industrialized countries, there is increasing awareness of leptospirosis as the cause of disease among inner-city populations, military personnel, and individuals engaged in swimming and water sports. Leptospirosis is an environmentally transmitted disease caused by spirochetes belonging to forty-one pathogenic species (P1 and P2) of the genus leptospira. Leptospirosis causes life-threatening disease in humans and domestic animals and has a major economic impact on livestock animals worldwide. To date, there is no effective prevention and control for leptospirosis. The major challenge has been developing a vaccine that protects against all the genetically diverse pathogenic species and >300 serovars which are potential agents for leptospirosis. All attempts to identify leptospiral vaccine candidates that can be used as a widely-applicable vaccine has failed. This crucial knowledge GAP has hampered the development of an effective universal vaccine that can provide synergistic health and societal benefits by preventing transmission and disease in domestic animals and the risk of spill-over infections in humans. Our work has been focused on closing those gaps. Recently, we evaluated a motility-deficient mutant strain of leptospira and found that immunization with this attenuated strain conferred cross-protective immunity in experimental animals, with antibodies against proteins being immune-correlates for this cross-protection. Furthermore, a multi-recombinant protein construct based on four targets identified from our attenuated-vaccine model elicited cross-protection against death and renal colonization. In this proposal, we hypothesize that our multi-recombinant protein candidate induces a strong humoral immune response that correlates with cross- protection on multiple animal models. Further, we hypothesize that this cross-protection is determined by a strong immune response against specific B-cell epitopes conserved among pathogenic species of leptospira SPP. We will vaccinate hamsters, mice and rats and determine the efficacy of out recombinant-protein construct to elicit cross-protection for death and/or renal colonization, and characterize their immunogenicity based on B and T cell responses. We will then apply a high throughput, random bacterial peptide display technology and a cryo-EM- based approach to identify epitope binding specificities with single amino acid resolution. Those epitopes will be then validated and selected based on their immunogenicity and cross-protective characteristics among different strains of pathogenic leptospira SPP. To establish a universal multi-epitope construct against leptospirosis. The results obtained by the characterization of our multi-recombinant protein vaccine would expand the work to confirm that a universal vaccine against leptospirosis is feasible. We expect to identify a potential generalizable candidate for leptospirosis, which can be advanced for process development and clinical trials for human and veterinary use, yielding new intervention strategies for this important yet neglected infectious disease problem.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $751,736 | |
| Amendment | $764,616 | |
| Amendment | $77,757 | |
| Amendment | $77,757 | |
| Amendment | $745,570 | |
| Amendment | $745,570 | |
| Original award | $745,570 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Yale Univ | $121,443 | |
| Infinity Bio, Inc. | $11,000 | |
| Serimmune Inc. | $55,000 | |
| University Of California Irvine | $147,038 |
Quick answers
Who received award R01AI182354?
R01AI182354 was awarded to University Of Connecticut by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 16, 2024.
How much is award R01AI182354 worth?
$3,908,576 has been obligated on R01AI182354.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award