Promising Inhibitory Human Monoclonal Antibody Discovery in The Fight Against Zika
ZIKA virus infection of expectant mothers can have devastating consequences, particularly for the fetus, and yet at present no vaccine is available. At the beginning of this year, the Zika virus pandemic was declared a public health emergency of international concern by the World Health Organization (WHO), igniting a drive for global virus-related research. Now, researchers from the School of Medicine, Washington University, St Louis, Missouri, USA, and the School of Medicine, Vanderbilt University, Nashville, Tennessee, USA, have isolated a human antibody capable of fetal protection by placental blockade to its infection.
Prevalent in both French Polynesia (2014) and Brazil (2015), the zoonotic Zika virus is transmitted between hosts by mosquitos. Like rubella, toxoplasmosis, and cytomegalovirus, infection of pregnant mothers by this flavivirus can result in microcephaly, a birth defect characterised by fetal head malformation. Aiming to aid vaccine progress, co-senior author Dr Michael Diamond, Departments of Medicine, Molecular Biology, Pathology and Immunology, Division of Infectious Disease, Washington University, St Louis, Missouri, USA and team were able to isolate a subset of 29 human anti-Zika antibodies seen to target epitopes of the envelope protein, using blood samples obtained from infected human adults.
Following the observation of effects on several in vitro strains of Zika, researchers found that one in particular, termed ZIKV-177, was seen to recognise a unique quaternary epitope located at the envelope dimer-dimer interface, effectively neutralising five separate strains. Administration to pregnant female mice 1 day prior to and 1 day post-Zika infection supported their previous findings, as both mother and fetus were found to have reduced virus levels compared with control. Immunisation of lethally-infected male mice also led to a positive decrease in virus level.
Co-author Prof James Crowe, Jr., Director of the Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA, enthused, “These naturally occurring human antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses. We are excited because the data suggests we may have antibody treatments in hand that could be developed for use in pregnant women.” These promising results pave the way for the development of an antibody-based vaccine against Zika infection in the near future and highlights the importance of virus structure construct in rationale design.