Spanish vaccine MVA-B HIV immune response achieved 90%
A phase I clinical trial shows the effectiveness of the Spanish candidate immune-B ​​MVA preventive vaccine against human immunodeficiency virus (HIV). 90% of volunteers subject to compound, developed and patented by the Consejo Superior de Investigaciones Científicas (CSIC) has developed an immune response to viruses and 85% of them remained for at least a year. The safety and efficacy are described in two articles in the journals Vaccine and Journal of Virology .

In 2008, the MVA-B showed high efficacy in mice and monkeys and virus protection from simian immunodeficiency (SIV). This finding has led to the execution of clinical trial in 30 healthy volunteers, led by the Hospital Clínic de Barcelona and the Gregorio Maranon de Madrid. Thanks to its high immune response in humans, the team will start with the Network for AIDS Research clinical trials phase I HIV-infected volunteers to test its efficacy as a therapeutic vaccine.

Treatment success is based on the immune system can be trained to respond to virus particles and infected cells permanently. The researcher at the National Center of Biotechnology, CSIC Mariano Esteban, the compound responsible for the development, explains: "MVA-B has proven to be as powerful or better than the vaccines currently under study."

With regard to the safety of MVA-B, "side effects that have occurred are to be expected in any kind of vaccination, mainly of local injection site," says team leader Gregorio Marañón Hospital Dr. Juan Carlos López Bernaldo de Quirós. He adds: "There has been no adverse effect has compromised the health of the volunteers."

"The results should be interpreted with caution because the treatment has only been tested on 30 volunteers, but stimulates a strong response in most cases, it is early to predict whether the induced defenses prevent infection," he qualifies the doctor responsible research team Clínic, Felipe Garcia.

The origin of the weapon

In 1999, Stephen's research team began work on the preclinical development of MVA-B, which gets its name from its composition from the Modified Vaccinia virus Ankara (MVA). This is an attenuated virus used to eradicate smallpox and serves as a model for the investigation of multiple vaccines. The B subtype of HIV comes from fighting against the most prevalent in Europe.

The development of MVA-B is based on the introduction of four HIV genes ( Gag , Pol , Nef and Env ) in the genetic sequence of vaccinia. A healthy immune system reacts to MVA, and the HIV genes inserted into their DNA are not able to infect humans, which ensures the safety of clinical trial.

A total of 24 volunteers was treated with MVA-B while the other 6 received a placebo, according to a double blind process. The vaccine was administered in three doses intramuscularly at weeks 0, 4 and 16, from the beginning, and its effects in peripheral blood were evaluated until week 48 when the trial ended.

Combat Battalion

The inoculation of the vaccine in a healthy volunteer intends to train your immune system to detect and learn to combat these components of the virus. According to Stephen, "as if I'll show a picture of HIV to be able to recognize if it is in the future."

The principal cells of this experiment are T and B lymphocytes Are the soldiers responsible for detecting foreign substances that enter the body and send the necessary signal to destroy them. "Our body is full of lymphocytes, each scheduled to fight a pathogen different," says Stephen. Therefore, "it is necessary to subject them to a workout when it is a pathogen that can not overcome naturally, like HIV," he adds.

B lymphocytes are responsible for humoral immune response, which acts on antibody production of HIV particles before they enter and infect a cell. They are anchored to its surface structure and block it. Blood tests at week 48 of treatment revealed that 72.7% of treated volunteers maintain HIV-specific antibodies.

For its part, T cells control the cellular immune response, designed to detect and destroy HIV infected cells. To test their defensive response to the vaccine, measured the production of interferon gamma immune protein. The analysis performed at week 48 of treatment, 32 weeks after the last inoculation of the vaccine, revealed that the production by CD4 + and CD8 + vaccinated group is 38.5% and 69.2% respectively, vs. 0% control.

Action on several fronts

A portion of interferon gamma, the presence of a pathogen in the body produces other immune proteins (cytokines and chemokines), each of which tends to attack the enemy by a different front. When the defensive action of T lymphocytes is able to generate several of these proteins, such action is known as multipurpose. CSIC researcher notes: "The importance of multi-functionality is the ability of pathogens to develop resistance to the immune system attacks; large polyfunctional least resistance."

Defensive spectrum of action of T lymphocytes undergoing vaccination was measured in terms of its production of three other immune proteins. The results indicate that the vaccine generates up to 15 types of different populations of CD4 + and CD8 +. Of these, 25% of CD4 + and 45% of CD8 + are capable of producing two or more different immune proteins, demonstrating its multi-functionality.

Veterans

To be truly effective vaccine, apart from the defensive capacity of the immune system requires it to generate a lasting response against future attacks. To do this, the organism must be able to maintain a basic level of memory T lymphocytes. These cells generated following a first attack by a pathogen, are veterans who can operate for years by the agency prepared to respond to a new incursion of the enemy .

The analysis in individuals vaccinated at week 48 revealed that 50% of CD4 + and CD8 + were from memory effect. This finding is consistent with 85% of patients maintained their immune response at this point of the trial.

Stephen said: "The immune profile of MVA-B satisfies in principle the requirements of a promising vaccine against HIV, such as induction of antibodies and activation of key cells in defense against pathogens such as CD4 and CD8 T lymphocytes." Thus, the immune response induced by the vaccine could keep under control the infection, because "if the virus enters the body and try to express in a cell, the immune system ready to inactivate the virus and destroy the infected cell," he adds. According to CSIC researcher, "to be marketed, the genetic cocktail must pass all tests yet of future clinical trials in phase II and III".