Two of the formulations, a vaccine based on an inactivated Zika virus and a DNA vaccine using two Zika genes, had already proved effective in mice, according to a report by Brazilian and US researchers published inNature in late June (see Pesquisa FAPESP no. 245 for an account in Portuguese).
“These results are important because they show it’s possible to create protection against Zika in monkeys, whose immune systems are far more similar to our own than those of mice,” said Brazilian immunologist Rafael Larocca, a member of Dan Barouch’s team at Harvard Medical School’s Center for Virology & Vaccine Research (CVVR) in the US and one of the main authors of both papers, alongside CVVR colleague Peter Abbink.
In the latest tests, the researchers vaccinated monkeys with a single dose or an initial dose followed by a booster shot using one of three formulations: the two types tested previously (inactivated and DNA), plus a third possibility based on a recombinant adenovirus vector expressing the Zika pre-membrane and envelope proteins.
The formulation that provided the best protection was the one based on a killed Zika virus, developed by the Walter Reed Army Institute of Research in Maryland. The monkeys given this vaccine and then infected with Zika had no detectable viral loads in their blood, urine, cerebrospinal fluid or vaginal secretions.
“Protection as comprehensive as this is important because of the risk of sexual transmission,” said Jean Pierre Peron, a neuroimmunologist at the University of São Paulo’s Biomedical Science Institute (ICB–USP) and co-author of both published papers.
Until the start of this year, the only known mode of transmission was through the bite of an infected mosquito, especially Aedes aegypti, but in recent months, reports have suggested that sexual transmission, including oral sex, may play a more important role than researchers imagined. A number of cases have pointed to the possibility of transmission by semen. French researchers reported in August that a man’s semen still contained a significant viral load 93 days after infection.
In July, US researchers had reported the first case of sexual transmission from a woman to a man. “This is cause for concern,” said virologist Paolo Zanotto, also a researcher at ICB–USP and co-author of the papers.
Zanotto and Peron are members of the Zika Research Network (Rede Zika), a São Paulo State task force linking institutions, laboratories and scientists who are investigating the virus with FAPESP’s support.
In recent weeks, Zanotto has urged the Harvard group to conduct experiments in monkeys using different Zika virus and dengue virus isolates. “We need to find out whether these two different viruses interact and if so what the implications are,” he said.
In one of the experiments described in the Science article, the researchers also extracted antibodies against Zika from the blood of vaccinated monkeys and injected them into mice that had never had contact with the virus or vaccine.
The antibodies were potent enough to protect the mice against infection by Zika. “The protection afforded by antibodies transferred from one organism to another suggests it might be possible to develop passive immunization strategies along similar lines to the method used to protect the fetus in a mother infected by cytomegalovirus,” Zanotto said.
In the next few months, the researchers at CVVR plan to start tests in humans, especially with the formulation containing the inactivated virus. Healthy volunteers are being recruited in the US for Phase I clinical trials of two other possible DNA vaccines, one produced by the Department of Health’s National Institute of Allergy & Infectious Diseases (NIAID) and the other jointly by GeneOne Life Science and Inovio Pharmaceuticals.
The article “Protective efficacy of multiple vaccine platforms against Zika virus challenge in Rhesus monkeys” by Peter Abbink, Rafael A. Larocca et al. can be read at science.sciencemag.org/lookup/doi/10.1126/science.aah6157.