Evaluation of an OV-16 IgG4 Enzyme-Linked Immunosorbent Assay in Humans and Its Application to Determine the Dynamics of Antibody Responses in a Non-Human Primate Model of Onchocerca volvulus Infection

• Published in: The American journal of tropical medicine and hygiene 2018-01, Vol.99 (4), p.1041-1048
• Main Authors: Cama, Vitaliano A, McDonald, Circe, Arcury-Quandt, Alice, Eberhard, Mark, Jenks, M Harley, Smith, Jared, Feleke, Sindew M, Abanyie, Francisca, Thomson, Lakwo, Wiegand, Ryan E, Cantey, Paul T
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Helminth - blood; Antigens, Helminth - administration & dosage; Antigens, Helminth - biosynthesis; Antigens, Helminth - immunology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay - methods; Enzymes; Humans; Immune Sera - analysis; Immunoglobulin G - blood; Immunoglobulin M - blood; Microfilariae - immunology; Onchocerca volvulus - immunology; Onchocerciasis - blood; Onchocerciasis - diagnosis; Onchocerciasis - immunology; Onchocerciasis - parasitology; Primates; Recombinant Proteins - administration & dosage; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Sensitivity and Specificity
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.18-0132

Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the recombinant antigen OV-16 in children to demonstrate the absence of transmission. We report the performance characteristics of a modified OV-16 enzyme-linked immunosorbent assay (ELISA) and describe anti-OV-16 responses in serum samples from laboratory-inoculated nonhuman primates (NHPs) in relation to microfilariae (mf) in skin snip biopsies. This OV-16 IgG4 ELISA had sensitivity and specificity of 88.2% and 99.7%, respectively, as determined by receiver operator characteristic analysis using a serum panel of 110 positive and 287 negative samples from people infected with other filariae or other parasitic infections. Anti-OV-16 responses in inoculated NHP ( = 9) were evaluated at quarterly intervals for IgM and the four IgG subclasses. Enzyme-linked immunosorbent assay results showed a well-defined IgG4 reactivity pattern and moderate IgG1 antibody responses. Meanwhile, the reactivity by IgG2, IgG3, or IgM did not show a clear pattern. Temporal evolution of IgG4 reactivity was evaluated through monthly testing, showing that NHPs developed anti-OV-16 IgG4 on average at 15 months postinoculation (range: 10-18 months). The average time to detectable mf was also 15 months (range: 11-25). The OV-16 ELISA used in this study was robust and allowed the detection of IgG4 responses, which were observed only among animals with detectable mf ( = 5), four of which showed declines in antibody responses once mf cleared. These findings also confirmed that the most informative antibody subclass responses to OV-16 are IgG4.