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Principal Investigator: BALI PULENDRAN
Organization: STANFORD UNIVERSITY
Fiscal Year: 2024
Award: $2,168,222
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT – Overall Component
In the current proposal we will use a systems vaccinology approach to address two fundamental issues in
vaccinology. The first issue concerns the immunology of COVID-19 vaccines, which utilize novel platforms
(mRNA) or adjuvants (Matrix M used in the Novavax vaccine). The second issue is related to the role of the
microbiome on vaccine immunity. With respect to the first issue, despite the rapid development of COVID-
19 vaccines, there is a paucity of understanding about the mechanisms by which they induce innate and
adaptive responses. Furthermore, the nature of the immune response induced by mRNA vaccines in special
populations such as those with serious allergic disease is unknown. Interestingly, there have been reports
of rare but severe allergic reactions to vaccination, in individuals with an atopic background. Therefore, we will
assess immunity to the BNT162b2 vaccine atopic versus healthy subjects. In the case of the Matrix-M
adjuvanted recombinant COVID-19 vaccine developed by Novavax, there is a paucity of understanding of
immune mechanisms stimulated by the saponin-based Matrix-M adjuvant. We will analyze samples collected
from a Novavax sponsored clinical trial in South Africa.
The second theme of the proposal is focused on the impact of the microbiome on immunity to
vaccination in healthy adults. Our recent work involving antibiotics driven ablation of the microbiota has
highlighted an important role for the microbiome in modulating immune responses to vaccination with the
seasonal influenza vaccine. However, the immune response against seasonal influenza vaccine in adults
represents a recall response, because of prior exposure to influenza. The impact of the microbiome on a
primary immune response, such as the response to rabies vaccination, is unknown.
These two issues will be addressed in the following highly collaborative projects and cores: Project 1 (PI
Pulendran) will utilize a multi-omics approach to define innate responses driving adaptive immunity immunity
to vaccination. The signatures identified in this project will be correlated with antigen-specific T and B cell
responses assessed in Projects 2 (PI Davis) and 3 (PI Boyd), respectively. Project 2 will perform an in-depth
analysis of the dynamics of the antigen-specific T cell responses to vaccination. Project 3 (PI Boyd; Co-I
Nadeau) will perform an in-depth analysis of the dynamics of the antigen-specific B cell responses to
vaccination. The three projects will be assisted by 4 cores. The Administrative Core will support the
coordination efforts across the HIPC-Stanford Center. The Clinical Core (PI Nadeau) will ensure a
standardized approach in the recruitment and clinical characterization of human subjects in all studies; the
Data Management and Analysis Core (PI Khatri) will provide bioinformatics expertise, and the Human
Immune Monitoring Core (PI Holden) will support the projects by providing immune monitoring assays.
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