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

TL;DR

A vaccine targeting Onchocerca volvulus protects mice by using IgG antibodies, neutrophils, and the complement system to kill larvae.

Contribution

The study identifies a novel IgG-mediated, neutrophil- and complement-dependent mechanism of protective immunity against Onchocerca volvulus larvae.

Findings

Vaccination with Ov-FUS-1 and Advax-CpG adjuvant induced IgG-mediated protection against Onchocerca volvulus larvae.

Neutrophils were essential for larval killing, and their depletion eliminated vaccine-induced immunity.

Complement component C3 was required for vaccine-induced protection, suggesting a role in the immune mechanism.

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.

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