A new delivery strategy of the HIV vaccine seems to enhance the protective immune response in a preclinical model. The scientist from the La Jolla Institute for Immunology (LJI) found out that delivering an HIV vaccine over several days in small doses results in a stronger immune response compared to when the vaccine is given at once.
According to Shane Crotty, Ph.D., the leader of the study, a similar escalating dose method might be the best way to administer an HIV vaccine in future clinical tests. The study was published in the journal Cell on May 9th, 2019.
Once you get sick, your immune cells team up to eradicate the pathogen. The cells responsible for making antibodies, B cells, move to areas in your lymph nodes known as germinal centers. B cells expressing antibodies with the ability to join the pathogen are normally selected to survive by T follicular helper (TFH) cells. The B cells making the best antibodies advance to further rounds of mutating, getting tested and antibody refinement.
The germinal center acts as a gym and the B cells have to go back repeatedly to undergo several rounds of selection for better binding.
The B cells
The B cells generate antibodies binding to the machinery on the virus launching the infection so as to beat HIV. HIV is, however, tough. It has an outer protein shell recognizable by antibodies. The shell has decoy sites confusing to the immune system. TFH and B cells work towards targeting the decoy sites not knowing the antibodies will fail.
Crotty and his team compared 3 vaccine dosage methods to find out if one might prompt neutralizing antibody production. Study collaborators tested these methods in rhesus monkeys.
The researchers were in need of a window into the immune system. They took advantage of a new technique to extract small germinal center cells repeatedly from lymph nodes. This enabled them to see the occurrence of antibody refinement in real-time. The lymph nodes were left intact and able to keep on improving B cell response in the germinal center.
The team tested 3 immunization methods. They were;
- A traditional vaccine
- An ‘osmotic pump’ strategy
- An escalating dose strategy.
The animals received partial doses of the vaccine for 12 days.
The traditional vaccine resulted in a terrible immune response which was dominated by non-neutralizing antibodies.
The 2 slow release strategies resulted in more and better antibodies.
According to Crotty, changing the delivery of the vaccines rather than the vaccine itself can have successful dramatic results. The next step would be to design delivery strategies for practical clinical use worldwide.
We need to think outside the box to come up with vaccines against pathogens that are hard to neutralize including the sexually transmitted disease caused by HIV.
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- MONKEYS ‘PUMPED’ WITH HIV VACCINE FOR DAYS ARE BETTER PROTECTED AGAINST VIRUS, SCIENTISTS DISCOVER
- La Jolla Institute for Immunology. (2019, May 9). New HIV vaccine strategy ‘pumps’ the immune system. ScienceDaily. Retrieved May 12, 2019 from https://www.sciencedaily.com/releases/2019/05/190509142828.htm