# Impact of HIV-1 and Aging on Mucosal Vaccine Responses

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2021 · —

## Abstract

7. Project Summary/Abstract
Both advancing age and HIV-1 infection are associated with an increased frequency of infection, such as those
due to Streptococcus pneumoniae, and a higher rate of complications and death with these infections.
Vaccines are available to prevent a number of infections common in older adults, such as pneumococcal
pneumonia and blood stream infection. However, many older adults, particularly those with underlying
disease, and persons living with HIV-1 infection show a decreased frequency, magnitude, quality and function
of specific antibodies following pneumococcal vaccination, as well as clinical vaccine failure. Underlying these
defects may be limitations in responses to infection and vaccines in both blood and at mucosal sites, where
most infections, such as pneumococcal pneumonia, begin.
Responses to vaccines begin quickly after immunization. We focus on the distinct events at the initiation of
immune responses to a newer pneumococcal vaccine directed against the polysaccharide capsule (PCV-13).
We study the initial generation of both T cell and B cell responses transiently identified in blood at 7 days after
immunization that reflect the key early events occurring in the lymphoid germinal centers. T cell subsets, such
as T follicular helper and regulatory cells (TFH and TFR, respectively) that promote and modulate B cell
activation and differentiation, are mobilized and circulate in blood. These T cells regulate a key protein
expressed in B cells, AID (activation-induced cytidine deaminase) that drives B cells to undergo antibody class
switch recombination (CSR) from IgM to IgG and IgA and to undergo affinity maturation by somatic
hypermutation (SHM). SHM enhances the avidity and function of these antibodies. Both TFH and AID activity
may be compromised in both aging adults and those with HIV-1 infection, potentially causing additive immune
compromise. We will study 80 adults, 40 with and 40 without HIV-1 infection, half of whom are 21-40 years of
age, half 55-64 to distinguish the contributions of both states to the integrity of vaccine responses. The work is
unique in characterizing antibody levels and quality at two relevant mucosal sites before and after vaccine - in
the nasopharynx where colonization begins, in the lung where pneumonia begins, and in the blood, where
invasive infections progress from initial mucosal sites, so effective mucosal defense is essential for protection.
The end point of vaccination is to generate antibodies of high avidity (strength of binding) and function
(opsonophagocytosis). We characterize these outcomes, the impact of aging and HIV-1 infection on acute TFH,
TFR and AID activation, and their impact on the early response of antibody-secreting cells specific for the
vaccine and the molecular basis of antibody quality which is determined by immunoglobulin gene mutations.
By identifying the specific defects associated with aging and HIV-1 infection, we propose to direct development
of...

## Key facts

- **NIH application ID:** 9856943
- **Project number:** 5I01CX001464-04
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Edward N Janoff
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856943

## Citation

> US National Institutes of Health, RePORTER application 9856943, Impact of HIV-1 and Aging on Mucosal Vaccine Responses (5I01CX001464-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856943. Licensed CC0.

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