Science and Technology

New technique opens the way for vaccines against HIV and other viral diseases

Researchers at the National Institutes of Health mapped the mechanism of action of neutralizing antibodies to HIV

Foto: NIAD
Anthony S. Fauci, diretor do National Institute of Allergy and Infectious Diseases (NIAID)
Anthony S. Fauci, diretor do National Institute of Allergy and Infectious Diseases (NIAID)

Researchers have described in detail how to evolve certain powerful antibodies capable of neutralizing HIV. The discovery raises vital clues to guide the design of a vaccine. The study was conducted by a team led by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

"This research brings us one step further to find an HIV vaccine and provides a powerful new technique for assessing the human immune response to experimental vaccines, not only for HIV but for pathogens in general," said NIAID Director Anthony S. Fauci.

The new results are based on the discovery made last year, reported by scientists at the VRC, three antibodies against HIV, two of which could prevent over 90% of global strains of HIV known to infect human cells in the laboratory. Called VRC01, and VRC02 VRC03, these antibodies were found in the blood of a donor in North America infected with HIV known in medical literature as a donor 45, whose body naturally produces these antibodies. In the new paper, scientists report the discovery of antibodies similar to VRC01 in the blood of two HIV-infected Africans known as the Giver, the giver 74 0219.

The researchers also found that these antibodies are similar to VRC01 attach to the same point of the HIV virus and in the same way. This suggests that a vaccine against the virus should contain a local replica of this protein, known as CD4 connection point, to obtain antibodies as powerful as the VRC01, according to the researchers. The point of attachment of CD4 is a few parts of the constantly changing virus that remains the same in HIV variants worldwide, this point and the virus uses to bind to cells it infects.

Scientists had already discovered that genes for antibodies similar to VRC01 suffer a surprisingly high number of mutations (from 70 to 90) between the first project, which encodes an antibody weak, and the final version, which encodes an antibody capable of neutralizing the HIV. These genes are found in the DNA of B cells of the immune system.

"To make a vaccine that induces antibodies similar to VRC01, we need to train the B cells to evolve the genes of their antibodies over a several ways to identify now, from childhood to a mature form of HIV," said VRC Director Gary J. Nabel.

To guide the B cells throughout this long evolutionary path, scientists first needed to map the route. They started with an existing technology to sequence genes of B cells that encode all the antibodies created by the immune system of a person. This study marks the first time this technology, called deep sequencing was used to monitor the antibody response to HIV at the genetic level. The researchers then developed sophisticated techniques of bioinformatics to decipher the large library of genetic data produced by the sequencing depth.

"We found a way to read books, or genes, this library by defining unique characteristics of antibodies similar to VRC01," said the head of structural biology of the VCR, Peter Kwong.

Based on the discovery of the structure of common genetic origin of antibody similar to VRC01, scientists have devised strategies to digitize the libraries of DNA from the donor B cells 45 and 74.

Next, the researchers focused on the segment of the gene that encodes the antibody part of VRC01 similar to that binds to and neutralizes HIV. Analyzing this sequence in the genes of the relatives revealed VRC01 newly discovered as a result has changed, step by step from the original state to a mature form. A vaccine that induces antibodies similar to VRC01 need to persuade the DNA of immature B cells of antibodies to evolve along one of these ways.

Scientists now plan to create proteins that they can offer by way of a vaccine to serve as indicators that guide the development of the B cell's DNA for the production of antibodies similar to VRC01. The new research has broad implications for vaccine development.