Novel b. Pertussis vaccines that elicit mucosal immunity
Ended Project Grant Awarded Last action
- Award ID
- R56AI183683
- Recipient
-
The Ohio State University UEI DLWBSLWAJWR1 Part of The Ohio State University
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $657,506
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Place of performance
- Ohio, USA
Award details come from USAspending.gov.
Description
- Abstract
- Despite high global vaccination rates, pertussis caused by the gram-negative bacterial pathogen bordetella pertussis (BP) is RE-emerging in vaccinated individuals. This is correlated with the switch in the 1990S from whole cell (WPV) to acellular vaccines (APV). WPV elicit TH1/TH17 polarized immune responses and clear BP from the entire respiratory tract. In contrast, APV elicit TH2 polarized immunity and do not prevent nasal colonization. Thus, APV immunized individuals serve as reservoirs for transmission to vulnerable populations. While the importance of CD4+ t cells for long-term protection against BP infection is established, the antigens recognized by the t cells remain undefined. Using high dimensional mass spectrometry and functional t cell assays we identified several new antigens from BP that generate tissue-resident memory t cell responses in mice and are recognized by CD4+ t cells from WPV immunized people. In this application we will test the efficacy of a subunit vaccine containing these antigens and the TH1/TH17 polarizing adjuvants bordetella colonization factor a (bcfa) and double mutant heat-labile toxin (dmlt). These adjuvants activate immune responses through different mechanisms and elicit mucosal immunity. We hypothesize that these vaccines will elicit long-lived TH1/TH17 tissue-resident t cell responses in the nose and lungs, and clear BP from the nose, thereby reducing the likelihood of BP transmission by vaccinated individuals. Specific aim 1: to test the ability of an intranasal subunit booster vaccine containing new t cell recognized antigens to reduce BP colonization in APV primed adult mice. We will test an intranasal (i.n) booster vaccine containing the TH1/TH17 polarizing adjuvant bcfa, admixed with detoxified pertussis toxin and three new t cell antigens, in mice previously immunized intramuscularly (i.m) with an approved APV. The systemic and mucosal t cell and antibody responses will be quantified, along with the phagocytes recruited to the respiratory tract, and the BP bacterial load in the nose and lungs. Specific aim 2: to test the immunogenicity and protective efficacy in infant mice of a subunit vaccine delivered by a heterologous immunization regimen. We will test the novel t cell antigens combined with the adjuvants dmlt and bcfa, separately and together. Vaccines containing dmlt will be tested by the i.d route and vaccines containing bcfa will be tested by the i.d or i.n route. Immune responses, bacterial load and the longevity of protection will be determined. Impact: there is a critical need for next generation pertussis vaccines that elicit mucosal immunity and prevent nasal colonization. The proposed experiments will test a vaccine formulation containing novel MHC class II presented antigens that will provide sustained protection against BP infection as a booster and as a pediatric vaccine. These foundational studies will lead to a safe and effective next generation pertussis vaccine that will prevent transmission and thereby reduce the burden of the disease pertussis.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $657,506 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Administrators Of Tulane Educational Fund | $16,417 |
Quick answers
Who received award R56AI183683?
R56AI183683 was awarded to The Ohio State University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 6, 2024.
How much is award R56AI183683 worth?
$657,506 has been obligated on R56AI183683.
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