# Using the Collaborative Cross to Discover New Requirments for Vaccine-Induced Immunity to T. gondii

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, MERCED · 2020 · $148,579

## Abstract

PROJECT SUMMARY
Immunological memory is the ability of our immune system to respond with greater strength and quickness
upon re-encounter with the same pathogen (i.e. secondary infection). Immunological memory is the basis for
vaccination which remains the most successful method for preventing infectious disease. Yet, a fully protective
vaccine that prevents a single human parasitic disease has not been realized to date. Why is immunity to
parasitic pathogens so difficulty to achieve? Our current work on secondary infections with the
apicomplexan parasite, Toxoplasma gondii, suggest that failure of immunological memory responses is
genetically determined. In this grant submission, we show unpublished data demonstrating the utility of using
recombinant inbred panels to discover new requirements for immunity to T. gondii. However, which genes and
immune responses are required for immunity against highly virulent strains of T. gondii are not fully
understood. We hypothesize the collaborative cross will reveal novel genes previously unknown to be
required for immunity to challenge with virulent strains of T. gondii. From published and unpublished
work in this system, we predict novel alleles segregating within the CC panel will promote CD8 T cell IFNγ-
responses during secondary infection and the generation of class switched antibodies with superior capacity to
recognize T. gondii. Experimental approaches from immunology, genetics and molecular parasitology will be
utilized to test these hypotheses. In Aim 1, the CC panel will be screened to identify loci that determine
immunity to virulent challenge, and whether identical loci control protective T and/or B cell immune responses
during challenge. In Aim 2, a combination of genetic and transcriptomic approaches will be implemented to
confirm and characterize how novel genes and alleles within the CC impact immunity to T. gondii. With the
overarching goal of preventing human toxoplasmosis, insights gained from this R21 proposal will guide future
projects on vaccination protocols that best prevent toxoplasmosis in susceptible mice.

## Key facts

- **NIH application ID:** 9961495
- **Project number:** 5R21AI145403-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Kirk David Christian Jensen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,579
- **Award type:** 5
- **Project period:** 2019-06-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961495

## Citation

> US National Institutes of Health, RePORTER application 9961495, Using the Collaborative Cross to Discover New Requirments for Vaccine-Induced Immunity to T. gondii (5R21AI145403-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961495. Licensed CC0.

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