Vaccine against respiratory syncytial virus is tested in humans

Results of phase 1 trials of vaccine developed in Belgium presented during FAPESP/EU-LIFE Symposium on Cancer Genomics, Inflammation & Immunity.

By Karina Toledo  |  Agência FAPESP – An experimental vaccine against respiratory syncytial virus (RSV) developed at the Flanders Inter-University Institute for Biotechnology (VIB) in Belgium is beginning the first phase of clinical trials.

In partnership with Canada’s Immunovaccine Inc., the university is testing the vaccine in 40 healthy adults to evaluate its safety. The first 20 volunteers who received it did not display any adverse reactions. In the preclinical phase, the experimental vaccine induced a hundredfold reduction of viral load in rodents.

The results were presented on June 8 at FAPESP’s headquarters in São Paulo, Brazil, by Xavier Saelens, a researcher at VIB. His presentation was part of the FAPESP/EU-LIFE Symposium on Cancer Genomics, Inflammation & Immunity, held to bolster collaboration between scientists in São Paulo State and Europe.

“RSV is one of the main causes of infection in the respiratory tract and lungs in newborns and small children and can cause bronchiolitis. It’s estimated that 200,000 children die from such infections every year worldwide, and more than 3 million are hospitalized. There’s a clear need for a vaccine,” Saelens said in an interview with Agência FAPESP.

According to Saelens, several groups have tried to find an antigen capable of inducing an effective immune response to the virus, but none has so far succeeded.

“At my lab, we’ve studied the 11 proteins encoded by this virus,” he said. “Some are very small and typically neglected by our immune system. To be honest, they’ve also been overlooked by researchers in the field. Three of these proteins are found in the membranes of infected cells and are accessible to our defense system. We decided to focus on one of them, known as the extracellular domain of the small hydrophobic protein, or SHe.”

In experiments with mice and rats, the Belgian group showed that the antigen induced a response capable of protecting against RSV. Although it did not completely eliminate the virus from the organism, it sharply reduced viral replication, giving the host organism more time to develop an adaptive immune response sufficient to eradicate the pathogen.

“The protein SHe helps the virus hide from the host’s immune system,” Saelens said. “But it’s interesting that when we analyzed infected animals and humans exposed to RSV, we didn’t find a clear response to this target. So we thought we would induce an immune response from which the virus hasn’t evolved a way of hiding.”

The mechanism of the vaccine’s action was elucidated in the preclinical phase and described in an article published in the journal EMBO Molecular Medicine. According to Saelens, the preliminary results of phase 1 clinical trials show that the vaccine is well tolerated by the human organism.

In the next step, the vaccine will be tested for safety in a larger number of volunteers and will also be assessed in terms of its capacity to induce a lasting immune response.

Brazilian drug candidate

Other research projects presented at the symposium held by FAPESP and EU-LIFE, an alliance of life science research centers located in 13 European countries, included one on the mechanism of a promising drug candidate called P-MAPA (protein magnesium ammonium phospholinoleate-palmitoleate anhydride), which displayed action against tumors and infectious diseases in preclinical trials.

Discovered over 50 years ago by Brazilian physician Odilon da Silva Nunes, the compound has been studied recently by members of Farmabrasilis, a non-governmental not-for-profit network of Brazilian, Chilean, European and US scientists established in 2001.

“Using animal models for bladder cancer, we were able to produce a complete description of the action mechanism of the immunomodulator P-MAPA,” said Wagner José Fávaro, a researcher affiliated with the University of Campinas’s Biology Institute (IB-UNICAMP) in São Paulo State.

According to Fávaro, the drug activates toll-like receptors in cell membranes, especially subtypes 2 and 4, inducing an immune response mediated by the cytokine interferon-gamma and stimulating production of the protein p-53. The combination of these effects induce the death of tumor cells.

“Activation of toll-like receptors and p-53 by P-MAPA triggers production of a type of collagen called endostatin, which reduces the formation of new blood cells and hence deprives the tumor of nourishment. Secondarily, the compound regulates the receptors of the sex hormones androgen and estrogen, thereby altering the metabolism of tumor cells. These effects help the immune system recognize and combat the tumor,” Fávaro said.

According to Iseu Nunes, CEO of Farmabrasilis, clinical trials of P-MAPA for the treatment of non-muscle invasive bladder cancer will begin soon (read more in Portuguese at agencia.fapesp.br/22905).

Another speaker at the symposium was Stephan Preibisch, a German researcher at the Berlin Institute of Medical Systems Biology (BIMSB) who has used a new technique known as light-sheet microscopy in conjunction with computer modeling to investigate gene transcription regulation in the nematode Caenorhabditis elegans.

C. elegans is considered a model organism for research of various kinds because it has a short lifecycle, its genome has been fully sequenced, and 60% of its genes are homologous with those of other eukaryotic organisms.

“Using this new technique, light-sheet microscopy, we can view entire organisms at high resolution and track living cells throughout their development,” Preibisch said. “This opens up the possibility of asking completely innovative questions.”

More information on the research projects presented during the FAPESP/EU-LIFE Symposium on Cancer Genomics, Inflammation & Immunity can be found at agencia.fapesp.br/23507.