# Role of antigen valency and pattern recognition receptor ligands in HPV vaccine-induced durable B cell memory

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $234,750

## Abstract

ABSTRACT
Most vaccines protect by generating antibodies. Live attenuated vaccines induce lasting humoral immunity;
however, humoral immunity for many subunit vaccines wanes over time. Because live attenuated vaccines may
not be feasible for all pathogens or recipients, the development of subunit vaccines that elicit potent and long-
lived antibody responses is essential. Vaccinology has focused for decades on developing subunit vaccines that
elicit robust and/or broad antibody responses to human pathogens. However, it is crucial to public health that
subunit vaccines also generate durable antibody responses. Thus, basic research is needed to know how to
reliably design such vaccines. The highly effective 9-type human papillomavirus subunit vaccine (HPV-9)
protects against nine HPV types that commonly cause cancer (e.g., HPV 16). Moreover, its antibody durability
is superior to that of many other approved subunit vaccines. Thus, HPV-9 represents a model subunit vaccine
for studying the generation of robust and enduring antibody responses. Unlike most other subunit vaccines, HPV
vaccines are comprised of a highly repetitive, high valency antigen: virus like particles (VLP). Each VLP HPV
type assembles from 360 units of its major capsid protein, L1. In addition, L1 binds DNA, and HPV-9 contains
recombinant L1 DNA. Whether high antigen valency or antigen-associated DNA generally enhances the
formation of durable B cell memory is not well studied. With regard to HPV, L1 VLPs elicit higher peak neutralizing
antibody responses than L1 pentamers and anti-VLP antibody responses depend on MyD88, a component of a
DNA sensing pathway. What is lacking is an understanding of whether vaccine DNA enhances the magnitude of
antibody responses to HPV-9 and whether antigen valency or vaccine DNA plays a role in the induction of
durable HPV-specific B cell memory. This proposal will address those gaps through two aims. The first aim is to
test the dependency of peak and long-lived HPV-9-elicited B cell responses on DNA sensors. Wildtype mice and
mice deficient in various DNA sensing pathways will be immunized with HPV-9 or alum. Before and at various
time points after each HPV-9 dose, HPV-specific neutralizing antibody, memory B cell, and bone marrow plasma
cell responses will be analyzed. In this way, the role of DNA sensing in stimulating peak, recall, and long-term
(≥12 months) B cell responses will be assessed. The second aim is to evaluate the dependency of long-lived
HPV-specific B cell memory on antigen valency. Mice will be immunized with three doses of monomeric HPV 16
L1 (1-mers), HPV 16 L1 pentamers (5-mers), or HPV 16 L1 VLPs (360-mers). Before and at various times after
each antigen dose, HPV 16-specific neutralizing antibody, germinal center B cell, memory B cell, and bone
marrow plasma cell responses will be analyzed. Responses to 1-mer, 5-mer, and 360-mer antigens will be
compared. In this way, the role of antigen valency in the induction of long-term...

## Key facts

- **NIH application ID:** 10510115
- **Project number:** 1R21AI171501-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Erin M Scherer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,750
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510115

## Citation

> US National Institutes of Health, RePORTER application 10510115, Role of antigen valency and pattern recognition receptor ligands in HPV vaccine-induced durable B cell memory (1R21AI171501-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10510115. Licensed CC0.

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