# Statistical Methods for Efficacy Trials of Vaccines and Monoclonal Antibodies Against Genetically-Diverse Pathogens

> **NIH NIH R37** · FRED HUTCHINSON CANCER CENTER · 2024 · $536,488

## Abstract

PROJECT SUMMARY (See instructions):
Safe and efficacious vaccines are needed to massively reduce the economic and human health costs of
HIV-1/AIDS, dengue, malaria, and COVID-19. This goal has been hindered by the genetic diversity of the
etiological pathogens. Randomized, controlled trials that rigorously assess the efficacy of candidate
vaccines to prevent infection and/or disease caused by these pathogens are a core research platform for
improving vaccines. Moreover, randomized efficacy trials of broadly neutralizing monoclonal antibody
(bnAb) regimens aid vaccine development. This project develops statistical methods for vaccine and bnAb
prevention efficacy trials, with purpose lo rigorously characterize multiple types of distinct and
complementary "immune correlates," which are critical tools for driving the iterative research process for
improving vaccines. Aim 1 develops methods for assessing immune markers measured over lime as
correlates of instantaneous risk of acquisition of HIV-1 or SARS-CoV-2 (of any strain or with a strain with
a particular feature such as an amino acid (AA) sequence or neutralization phenotype) in (a) HIV-1 and
COVID-19 vaccine and (b) HIV-1 bnAb efficacy trials. Aim 2 develops methods for assessing immune
markers measured by a fixed time point post-vaccination in HIV-1, dengue, malaria, and COVID-19
vaccine efficacy (VE) trials as multiple types of correlates of protection: (a) an estimated optimal surrogate
a summary marker combining information from all markers that best predicts overall or feature-specific
outcome; (b) a correlate of VE la marker that modifies VE, studied via the statistical frameworks principal
stratification, controlled causal effects, and stochastic interventional causal effects. Aim 3 develops
dynamic recurrent event models for assessing (a) malaria VE against overall and circumsporozoite protein
(CSP) AA-specific malaria infection and disease, and (b} how CSP AA-specific malaria risk depends on
prior malaria infections and vaccination. Aim 4 develops causal methods for assessing vaccine and bnAb
efficacy to prevent (a) overall and (b) feature-specific HIV-1 acquisition in study populations defined by
certain patterns of pre-exposure prophylaxis use. The methods are developed with application lo 14
recently completed or ongoing VE trials (4 for HIV-1, 2 for dengue, 2 for malaria, 6 for COVID-19) and 2
HIV-1 bnAb efficacy trials. Collectively, the aims advance development of immune correlates based on
both immune marker data and pathogen genetic sequence/immunophenotype data.

## Key facts

- **NIH application ID:** 10774815
- **Project number:** 4R37AI054165-23
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Peter B. Gilbert
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $536,488
- **Award type:** 4C
- **Project period:** 2003-04-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10774815

## Citation

> US National Institutes of Health, RePORTER application 10774815, Statistical Methods for Efficacy Trials of Vaccines and Monoclonal Antibodies Against Genetically-Diverse Pathogens (4R37AI054165-23). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10774815. Licensed CC0.

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