November 7, 2016

expert reaction to study reporting results of antibody therapy in pregnant mice with Zika

Using samples from patients previously infected with the Zika virus, a group of scientists writing in the journal Nature have reported the identification of antibodies which were able to mitigate the effect of infection in pregnant and non-pregnant mice.

Dr Derek Gatherer, Lecturer in the Division of Biomedical and Life Sciences, Lancaster University, said:

“This work describes some important progress in our understanding of Zika and how we might treat it in pregnancy. It also raises some questions which will need to be addressed before we arrive at that treatment.

“Antibodies were first purified from human Zika patients – these are monoclonal antibodies, meaning that each one has a very specific target on the Zika virus particle. These monoclonal antibodies were then administered to pregnant mice previously injected with Zika virus. The mouse model of Zika infection is not quite the same as a ‘natural’ Zika infection in humans – mice are normally resistant to Zika, so they have to be given a strain of the virus which is specially adapted to grow in them, and also an immunosuppressive treatment to prevent them fighting the virus as efficiently as they otherwise might. Mice treated in this way will give birth to pups that show some signs of brain and nervous damage by Zika, as well as other abnormalities similar, if not exactly identical, to those found in humans.

“The monoclonal antibodies purified from the human survivors are shown to protect the mice. It will be a while, however, before we feel confident enough to try this treatment on humans. The authors note that we really need to repeat the experiment in monkeys, since their pregnancies are more similar to ours and, unlike mice but like humans, they are naturally susceptible to Zika.

“The authors also make some interesting observations in passing that are highly relevant to vaccine development in humans, and also our future expectations of what effects Zika might have in Africa and Asia. The first of these is that they note that some anti-Zika antibodies cross-react with Dengue virus. This is of concern since Dengue Shock Syndrome, the fatal form of Dengue infection, occurs when people previously exposed to one strain of Dengue are exposed to a different one, and a hypersensitivity reaction can take place. We would really need to be certain that delivering a dose of anti-Zika antibody (if it was also effectively functioning as an anti-Dengue antibody too) to a person previously infected with Dengue (and very many have been in the tropical world), would not produce some kind of Dengue Shock Syndrome-type reaction.

“The second interesting tangential observation is that the anti-Zika antibodies protect against all strains of Zika, whether African, Asian or American. This is good news, as it suggests that many people in African and Asia will already be effectively immune to Zika from the Americas, and lessens the concern that Zika will cause similar problems in Africa and Asia as it already has in Brazil.”

‘Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice’ by Gopal Sapparapu et al. published in Nature on Monday 7 November 2016. 

Declared interests

Dr Derek Gatherer: “Derek Gatherer has no conflict of interest relevant to the subject of Zika virus.”