Study may reveal how Zika causes brain damage
AGÊNCIA FAPESP/DICYT Researchers at the University of São Paulo’s Biomedical Science Institute (ICB-USP) in Brazil have found a molecule in pregnant mice that, when inhibited, causes a reduction in the effects of Zika virus on the nervous system of their offspring, including microcephaly.
The proposed therapy, which is still in the experimental stage, was presented to the São Paulo School of Advanced Science (SPSAS) in Vaccines, held with FAPESP’s support at Santos on the coast of São Paulo State from November 22 to December 2, 2018.
“When we treated the contaminated pregnant mice with an inhibitor of this molecule, we succeeded in considerably reducing the number of viruses that reached the fetus. In addition, fetal and neonatal skull size increased,” said Jean Pierre Schatzmann Peron, a professor at ICB-USP and principal investigator for the study. A paper has been submitted to a high-impact scientific journal, but publication has not yet been scheduled.
The mechanisms of the diseases and proposals for the development of new vaccines and therapies were among the topics discussed during the SPSAS, which was attended by 72 students from Brazil and 19 other countries, as well as 22 Brazilian researchers and colleagues from institutions in Australia, Italy, Japan, the United Kingdom and the United States.
“The SPSAS presented a diverse and up-to-date program on vaccines. It began with the basics, such as innate immunity, adaptive immunity and dendritic cells. As the course progressed, the topics became more complex. Part of the second half was devoted to clinical trials. We ended with systems vaccinology. The speakers we invited had expertise in these different areas,” said Irene da Silva Soares, Full Professor in the University of São Paulo’s School of Pharmaceutical Sciences (FCF-USP) and one of the organizers of the School.
“Despite major progress in recent years in studies on vaccines against HIV, malaria, leishmaniasis, Chagas disease and others, it’s still a daunting challenge to develop vaccines for these diseases. Recent outbreaks of diseases like Zika have given researchers in this field a jolt, and they’ve achieved significant advances, but the end result in terms of new vaccines on the market isn’t satisfactory yet,” Soares said.
Considerable progress has been achieved in producing a Zika vaccine, which is now at an advanced stage of development. After publishing the first results in an article in Nature in 2016, a team led by Brazilian immunologist Rafael Larocca at Harvard Medical School’s Center for Virology and Vaccine Research (CVVR) in the US reached the stage of Phase II clinical trials in humans.
“What remains to be done to release the vaccine to the market is effectiveness testing, which means testing the vaccine in areas where the disease is endemic and people are known to be exposed to the virus,” said Larocca, who earned a master’s degree and PhD from the University of São Paulo (USP) with scholarships from FAPESP. “The problem is that the virus is no longer circulating, so this last part of the tests can’t be done.”
In his presentation, Larocca also detailed the results of an unpublished study showing that the vaccine developed by his laboratory protected not only pregnant mice but also their fetuses. Moreover, six months after administration of the vaccine, the mice gave birth to pups that were immune to the virus. “The initial results show protection passing not only from the mother to the fetus in utero but also to the newborn offspring,” he said.
According to Soares, the presentations highlighted the significant challenges of new vaccine development. “The discussion focused on vaccines that use new strategies, such as those based on proteins or recombinant viruses, and DNA vaccines,” she said.
Other speakers at the School included Gabriel Victora from The Rockefeller University (USA); Nigel Curtis from the University of Melbourne (Australia); Arturo Reyes Sandoval from the University of Oxford (UK); Rino Rappuoli from GlaxoSmithKline (GSK); Silva Boscardin from ICB-USP; and Ricardo Gazzinelli from Fiocruz and the National Institute of Science and Technology in Vaccines (INCT-V).