Brazilian researchers announce clinical trials for dengue vaccine

Recruitment of volunteers began on October 2, with the objective of verifying the vaccine’s safety and the immune response it produces.

By Noêmia Lopes

Agência FAPESP – The Butantan Institute and the Universidade de São Paulo School of Medicine (FMUSP) announced on October 2 the recruitment of volunteers for clinical trials of a tetravalent vaccine against the four known types of dengue (1, 2, 3 and 4).

Composed of weak strains of live viruses, the vaccine was created by researchers at the National Institutes of Health (NIH), and tests in animals and humans were successful. The tests showed that the vaccine was safe, with few side effects (pain and redness at the injection site), and efficient in inducing the production of antibodies after administration of a single dose.

Alexander Precioso, director of the Division of Clinical Trials and Pharmaco-surveillance at Butantan Institute, explained, “NIH made the vaccine available through a partnership with the Butantan Institute for production and human trials in Brazil. The vaccine will be tested for the first time in an endemic region where dengue is an extremely relevant public health concern.”

“The American researchers proved that the mosquito carriers of dengue are not capable of spreading the weakened form of the virus and cannot transmit the disease from people immunized with the vaccine,” he added.

Esper Kallás, associate professor at the FMUSP’s Immunology and Allergy Clinic and coordinator of the test that will be conducted at the university’s Hospital das Clínicas, was also present at the press conference and affirmed that the objective is to confirm the results obtained in the United States.

“The phase of clinical development is certainly the most challenging and complex, but we believe that we have a promising product in hand,” Kallás said. “There are dengue vaccines in the production phases at other companies. But their vaccines have required more than one dose, while the initial results of the vaccine that we will test indicate the need for only a single dose.”

FAPESP supported production of the vaccine in Brazil through the research project Dengue: production of experimental batches of a tetravalent candidate vaccine against dengue. The Brazilian Develop Bank (BNDES) and the Butantan Foundation funded the clinical trials.

Screening and monitoring

The Brazilian Health Surveillance Agency (ANVISA) authorized the clinical trials, along with the ethics committee at USP’s Medical School, the National Committee on Research Ethics (Conep) and the National Technical Commission on Biosafety (CTNBio).

During screening, volunteers will be given lab exams and medical evaluations. In the first stage of the trials, the researchers will choose 50 participants – healthy men and women between the ages of 18 and 59 – who were raised in São Paulo and have never contracted dengue. This group will be monitored by doctors, nurses and pharmacists from FMUSP’s Hospital das Clínicas.

In the following phase, initially slated for the beginning of 2014, another 250 volunteers will be recruited, including some who have contracted dengue and some who have not. In this phase, the participants will be monitored by hospitals run by the USP Medical School in São Paulo (FMUSP) and the USP Medical School in Ribeirão Preto (FMRP).

In December 2014, the researchers expect to have all the necessary data to describe the safety profile of the vaccine and the immune response that it is capable of producing.

“Regardless of this deadline, the volunteers will be monitored for five years to verify the maintenance of the immune response over time and to better describe what the vaccine can afford from an immunological point of view,” Alexander Precioso said.

If the study develops as planned, beginning in 2015 the vaccine will be tested in cities in different regions of Brazil, resulting in the volume of information required to request its registration with ANVISA.

“Depending on our findings, it is possible that Butantan will make the vaccine available under the National Immunization Program beginning in 2018,” commented Precioso.

The Butantan Institute will be responsible for production of the vaccine, coordination of the clinical trials, and selection and training of researchers. In addition to USP and NIH, partners in the initiative include the Adolfo Lutz Institute, Johns Hopkins Bloomberg School of Public Health and Global Solutions For Infectious Diseases.

The volunteers will sign consent forms. Women who are pregnant, lactating or plan to conceive in coming months will not be allowed to participate in the trials.

More information is available at: www.vacinadengue.com.br.