Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX<sup>®</sup> Vaccine-Induced IgG Antibodies in Zambian Children
Cynthia Mubanga,
Michelo Simuyandi,
Kapambwe Mwape,
Kennedy Chibesa,
Caroline Chisenga,
Obvious Nchimunya Chilyabanyama,
Arlo Randall,
Xiaowu Liang,
Richard H. Glashoff,
Roma Chilengi
Affiliations
Cynthia Mubanga
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Michelo Simuyandi
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Kapambwe Mwape
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Kennedy Chibesa
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Caroline Chisenga
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Obvious Nchimunya Chilyabanyama
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Arlo Randall
Antigen Discovery Inc., 1 Technology Dr., Suite E309, Irvine, CA 92618, USA
Xiaowu Liang
Antigen Discovery Inc., 1 Technology Dr., Suite E309, Irvine, CA 92618, USA
Richard H. Glashoff
Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa
Roma Chilengi
Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia
Developing a broadly protective vaccine covering most ETEC variants has been elusive. The most clinically advanced candidate yet is an oral inactivated ETEC vaccine (ETVAX®). We report on the use of a proteome microarray for the assessment of cross-reactivity of anti-ETVAX® IgG antibodies against over 4000 ETEC antigens and proteins. We evaluated 40 (pre-and post-vaccination) plasma samples from 20 Zambian children aged 10–23 months that participated in a phase 1 trial investigating the safety, tolerability, and immunogenicity of ETVAX® adjuvanted with dmLT. Pre-vaccination samples revealed high IgG responses to a variety of ETEC proteins including classical ETEC antigens (CFs and LT) and non-classical antigens. Post-vaccination reactivity to CFA/I, CS3, CS6, and LTB was stronger than baseline among the vaccinated compared to the placebo group. Interestingly, we noted significantly high post-vaccination responses to three non-vaccine ETEC proteins: CS4, CS14, and PCF071 (p = 0.043, p = 0.028, and p = 0.00039, respectively), suggestive of cross-reactive responses to CFA/I. However, similar responses were observed in the placebo group, indicating the need for larger studies. We conclude that the ETEC microarray is a useful tool for investigating antibody responses to numerous antigens, especially because it may not be practicable to include all antigens in a single vaccine.
