Vaccination against Onchocerca volvulus induces IgG-mediated protective immunity dependent on neutrophils and complement.

Authors

• Nathan M Ryan
• Jessica A Hess
• Mohini Nakhale
• Annabel A Ferguson
• William Stump
• Sara Belko
• Rachel Monane
• Robert S Pugliese
• Nikolai Petrovsky
• Benjamin L Makepeace
• Sean A Gray
• Darrick Carter
• Sara Lustigman
• David Abraham

Publication/Presentation Date

10-22-2025

Abstract

Onchocerciasis remains a significant cause of morbidity and economic loss in sub-Saharan Africa. Despite the existence of effective therapeutics, a prophylactic vaccine targeting the etiologic agent, Onchocerca volvulus, is needed to control ongoing disease and transmission. Mice were vaccinated against O. volvulus with a fusion of the recombinant antigens Ov-103 and Ov-RAL-2 (Ov-FUS-1) with Advax-CpG adjuvant. Immunized mice developed protective immunity with the killing of third-stage larvae (L3) within 36 h of challenge infection. IgG from immunized mice passively transferred protective immunity to naïve mice, indicating that antigen-specific IgG mediated parasite elimination. Neutrophils were the most abundant subset of immune cells recruited to the parasite microenvironment in vivo, and treating mice with a granulocyte-depleting antibody resulted in the total loss of immune-mediated larval killing. Analysis of neutrophil gene expression revealed that both vaccination and the presence of O. volvulus larvae were capable of modulating neutrophil transcriptional activity. The mechanism by which antigen-specific IgG and neutrophils collaborated to kill L3 was independent of Fcγ receptors. However, the elimination of complement component C3 prevented vaccine-induced protection, which suggests these components may interact through the complement system. This study describes a vaccine-induced mechanism of protective immunity against O. volvulus L3 dependent on IgG, neutrophils, and complement, highlighting an effective collaboration between the innate and adaptive arms of the immune system to control O. volvulus infection.

Volume

10

Issue

1

First Page

221

Last Page

221

ISSN

2059-0105

Published In/Presented At

Ryan, N. M., Hess, J. A., Nakhale, M., Ferguson, A. A., Stump, W., Belko, S., Monane, R., Pugliese, R. S., Petrovsky, N., Makepeace, B. L., Gray, S. A., Carter, D., Lustigman, S., & Abraham, D. (2025). Vaccination against Onchocerca volvulus induces IgG-mediated protective immunity dependent on neutrophils and complement. NPJ vaccines, 10(1), 221. https://doi.org/10.1038/s41541-025-01267-x

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

41125576

Department(s)

Administration and Leadership

Document Type

Article