# Optimization and preclinical development of a TB Multiple Antigen Presenting System (MAPS) vaccine

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $1,153,542

## Abstract

Project Summary/Abstract
 The overall objective of the proposed research is to optimize and further the development of a vaccine
directed against Mycobacterium tuberculosis (Mtb) using a novel platform, the Multiple Antigen Presentation
System (MAPS) developed by the Malley laboratory at Boston Children’s Hospital (BCH). Most current
bacterial vaccines are based on enhancing the immunogenicity of polysaccharide (PS) capsular antigens
(which determine serotype in many bacteria) by chemical conjugation to proteins. These vaccines suffer from
limitations including an inability to elicit CD4+ Th1 or Th17 responses to antigens and high complexity of
manufacture. For several organisms, T cell responses (either alone or in conjunction with antibody responses)
are deemed necessary for mucosal or systemic protection. To overcome these limitations, we have developed
MAPS, a vaccine platform that confers comprehensive immunity by eliciting antibodies to the PS and proteins,
and CD4+ Th1 and Th17 responses to proteins. The technology is based on our discovery that proteins and
PS linked via the affinity interaction between biotin and rhizavidin behave like a conjugate protein-PS vaccine,
with the added benefit of generating robust CD4+ Th1 and Th17 responses to proteins.
 In preliminary studies, we have developed a TB MAPS vaccine composed of several Mtb proteins
scaffolded onto a non-Mtb PS (pneumococcus type 1) which shows significant protection against pulmonary
tuberculosis (TB) in a mouse model, particularly when combined with the live BCG vaccine; protection elicited
by the combination of TB MAPS and BCG given concurrently at separate sites followed by 2 TB MAPS
boosters is significantly greater compared to BCG or TB MAPS alone. Here, we will examine if protection by
this TB MAPS construct can be augmented by the inclusion of one of three Mtb-specific PS. Our preliminary
data strongly support the feasibility of this approach. To meet our goals, we have assembled a group of
investigators that are experts in vaccine development (Dr. Malley from BCH and Dr. Pavliak from the
International Vaccine Institute (IVI) in Korea, our industry partner) and tuberculosis research and animal
models (Dr. Rubin from Harvard School of Public Health and Dr. Kaushal from Tulane University). The project
will thus be a collaborative effort between investigators from academic institutions and a nonprofit agency with
extensive experience in vaccine development (IVI). In the proposed experiments, we will evaluate whether the
addition of Mtb PS to our current TB MAPS vaccine enhances protection in the mouse model, select the
optimal TB MAPS vaccine (i.e. with or without Mtb PS, the proteins having been already selected) and then
evaluate whether the combination of BCG given concurrently (at separate sites) with TB MAPS then followed
by two booster doses of TB MAPS is superior to BCG alone in a nonhuman primate model of tuberculosis. A
Product Development Plan has been prepared, ...

## Key facts

- **NIH application ID:** 10073328
- **Project number:** 5R01AI135720-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** RICHARD MALLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,153,542
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073328

## Citation

> US National Institutes of Health, RePORTER application 10073328, Optimization and preclinical development of a TB Multiple Antigen Presenting System (MAPS) vaccine (5R01AI135720-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073328. Licensed CC0.

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