Antibodies Identified in Zika-infected Individuals May Help Lead to a Vaccine

An international team of researchers has identified a potential role for certain monoclonal antibodies in developing a treatment for Zika virus, the mosquito-borne infection that continues to plague regions in South America the Caribbean and has been associated with birth defects in children born to infected mothers.

In a study published July 14 in the journal Science, scientists from Switzerland, Great Britain, the United States, Australia, Italy, and Vietnam isolated a panel of 119 monoclonal antibodies from 4 donors infected with Zika virus, 2 of whom had also been previously diagnosed with dengue virus infection. Dengue, like Zika, is a flavivirus. The selected monoclonal antibodies (primarily immunoglobulin G, highly polyclonal, and with few somatic mutations) in the study were derived from Epstein-Barr virus-immortalized memory B cells based on their binding to Zika virus non-structural protein 1 or E proteins.

The authors compared the selected monoclonal antibodies with a panel of monoclonal antibodies previously isolated from donors infected with the dengue virus. Of the 119 isolated monoclonal antibodies, the authors found that 41 bound to non-structural protein 1, which is secreted by infected cells and has been shown to be involved in immune evasion and pathogenesis in flaviviruses such as Zika. Indeed, in general, they found that antibodies to non-structural protein 1 were “largely Zika-specific,” revealing a possible diagnostic role in particular for the monoclonal antibody ZKA35, which, the authors found, binds to the antigenic site S2 in Zika virus and thus “has [the] potential to be developed in a serological assay to detect clinical and sub-clinical Zika virus infections at the population level.”

Conversely, their work found that antibodies against E protein domain I/II (EDI/II) in both viruses “were cross-reactive and, while poorly neutralizing, potently enhanced” both infections in vitro and “lethally enhanced dengue virus” in mice. Furthermore, they noted that memory T cells against non-structural protein 1 or E proteins were “poorly cross-reactive,” even among study donors pre-exposed to dengue.

According to their published findings, the most potent neutralizing antibodies were Zika-specific and targeted EDIII or “quaternary epitopes on infectious virus.” Importantly, they determined that the EDIII-specific monoclonal antibody ZKA64-LALA “completely protected A129 mice challenged with a lethal dose of Zika virus from body weight loss and lethality when given one day before or one day after [viral] challenge,” thus illustrating the potential for antibody-based therapy.

The authors were not available for comment at press time. However, in their concluding remarks, they note, “This study reports the first characterization of the human immune response to Zika virus infection. Our study describes two classes of potent neutralizing antibodies that are specific for Zika virus and directed either against EDIII or quaternary epitopes present on infectious virus, the latter being particularly frequent, similarly to what has been described in dengue virus. Given the high potency and in vivo efficacy shown in this study, these antibodies, developed in wild-type or their LALA versions to avoid possible enhancement, could be used in prophylactic or therapeutic settings to prevent congenital Zika virus infection in pregnant women living in high risk areas.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.