Management and treatment of HIV have been a hot topic of research for years. Even the researchers at Scripps Research are working for more than 20 years on designing HIV vaccine. The findings of this research study are published in the journal Immunity. It describes an experimental vaccine strategy that has been successful in non-human primates.
The study was performed on rhesus macaque monkeys. The research team tried to produce neutralizing antibodies against one strain of HIV that is similar to a resilient viral strain that attacks humans (called a Tier 2 virus). This research is a first time ever investigation of any vaccine-induced neutralizing antibody levels that may help protect from HIV.
The significance of this study
The research team found that neutralizing the antibodies through this experimental vaccination may save life against viral attack. Although the vaccine is far behind its clinical trials on humans but this study is a proof that HIV vaccine strategy may work someday.
The goal of this HIV vaccine developmental strategy is to identify the lethal strains and improve the human immune system to combat these viruses. The previous studies show that the body needs to produce certain anti bodies in response to the virus so they may bind to the virus’s envelope. To check it, the team of scientists at Scripps injected animals with neutralized antibodies developed in lthe ab.
challenges and problems
The challenge was to see how the immune system of these animals responds to the antibodies. For this, researchers exposed their immune system to the envelope protein trimer. This was a part of vaccine developmental strategy to effectively train the immune system on how to spot the target and produce the correct antibodies for it.
There was a huge problem that HIV envelope trimer was unstable and usually it falls apart when it is isolated. This way it was difficult for the scientists to use it in this vaccine production.
A research from 2013 showed that scientists have genetically developed a stable trimer or SOSIP for the first time in history. It looks so much like the original HIV envelope protein trimer, the researchers at Scripps Research and the first author of this study claim.
The next phase was to design an experimental vaccine with this genetically modified, highly stable SOSIP trimer. At this stage, the goal was to check if this genetically modified model protects the animal from HIV or not.
It was tested on two groups. A previous study on the same vaccine showed that some immunized animals naturally developed low neutralizing antibody titers in them and others developed high titers from a vaccine.
From this research, the team selected six low titer and six high titer monkeys for revaccination. Also, they examined 12 completely unimmunized primates calling them the control group.
These primates were exposed to a particular form of virus termed SHIV. This is an engineered simian version of HIV. It has more or less same envelope trimer as that of the human virus and is called Tier 2 virus. It is a hard strain to neutralize which is common for most of HIV circulating strains in human societies.
What did the results show?
The results showed that the vaccination worked for the group of high titer animals. These monkeys produced sufficiently high levels of neutralizing antibodies against the envelope protein trimer. This is the first ever evidence that a study has shown an antibody-based protection from a Tier 2 virus following vaccination, as the research team explains.
The next challenge to this vaccine is how to get such a high titer in every animal. This focus on titer is important as the HIV protection through vaccine works well in high titers.
The study also showed that neutralizing antibodies is the only way to stop the virus from causing disease. This is a different approach and many other labs are focusing on alternate protection systems mainly T cells and other immune system defenses to block the virus.
Going forward, the researchers are hopeful that an improved design of a vaccine for human trial on high titre may help in HIV. This strategy is helpful to elicit broadly neutralizing antibodies (bnAbs) that work against a majority of HIV strains for future.