# Enhancing B cell maturation and function using bisphosphonates in HIV

> **NIH NIH R03** · EMORY UNIVERSITY · 2021 · $78,000

## Abstract

PROJECT SUMMARY/ABSTRACT
People living with HIV (PLWH) and the elderly more susceptible to potentially fatal complications from influenza
(such as pneumonia) and invasive Streptococcus pneumoniae bacteremia and meningitis. Age-associated B cell
defects compound HIV-induced B cell dysfunction to severely compromise humoral immune responses to
influenza viruses and pneumococcus. Routine vaccinations against influenza and pneumococcus are therefore
recommended in these populations but antibody responses to these vaccinations are poor and ineffective.
Strategies to improve B cell function and boost humoral immune responses to infection and vaccination are
therefore needed to improve health outcomes for the aging HIV/AIDS population.
Bisphosphonates (BPs), inhibitors of bone resorption used in the treatment of skeletal disorders including
osteoporosis, unexpectedly improved humoral immune responses in mice and also increased total IgG levels in
humans with Paget's disease of bone. This suggests that BPs can act as B cell-targeting adjuvants to boost
antibody responses, but the mechanism is unknown. My ongoing K01 is leveraging this observation in a pilot
study to investigate if the BP Zoledronic Acid (ZA) can reverse HIV-induced B cell dysfunction and improve
antibody responses to infection and vaccination. Our data indeed reveal that ZA significantly boosted anti-
influenza A IgG antibody levels in immunized HIV-infected individuals (aged 30-50) by 32%, compared to only
8% in the placebo group. The mechanism underlying this boost in antibody responses and whether it occurs in
individuals PLWH >50 years old is unknown. Also, the ability of oral BPs such as Alendronate and Ibandronate,
which are even more widely used in clinical practice, to boost humoral immunity in PLWH, is unknown. The aim
of this R03 project is to gain a better understanding of the potential mechanisms by which BPs boost antigen-
specific antibody responses.
We will leverage samples from BP-treated and non-BP-treated HIV- and HIV+ male and female participants
enrolled in the NHLBI-funded Combined Cohort Study (CCS) to show that BPs boost humoral immunity to
clinically-relevant viral (influenza) and bacterial (pneumococcus) antigens by enhancing B cell maturation and
function. These studies extend my ongoing K01 project and add essential mechanistic endpoints to generate
robust data in support of my future R01 application investigating the molecular mechanisms of BP-mediated
enhanced humoral immunity in aging PLWH.

## Key facts

- **NIH application ID:** 10236544
- **Project number:** 5R03HL154829-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Kehmia Nubonyin Titanji
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2020-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236544

## Citation

> US National Institutes of Health, RePORTER application 10236544, Enhancing B cell maturation and function using bisphosphonates in HIV (5R03HL154829-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10236544. Licensed CC0.

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