CTL-based vaccines and HIV-1.
Quick recap– All of your cells fly ‘flags’ that show circulating cytotoxic T-cells what proteins they are making. Normally, a virus-infected cell will put up virus/pirate ‘flags’, the T-cell will ‘see’ something is wrong, and convince the infected cell to commit suicide. This process is thwarted by HIV-1 numerous ways, so infected cells arent killed. Some people can ‘see’ the HIV-1 ‘pirate flags’, so they (kind of) control HIV better, but HIV is evolving ways around this. As a whole, the HIV-1 population is evolving an entire branch of the human immune system.
We will not be able to make CTL-based vaccines against HIV if we dont start vaccinating, like, yesterday.
BUT! What if we dont try to train immune systems to look for HIV-1 pirate flags? Theres no point, right? What if we train the immune system to look for different, *self* flags that are inappropriately expressed due to the cell being infected with HIV-1? Self flags that cannot change the way HIV-1 can? Self flags like ERV proteins, which should not be expressed on normal, healthy cells, so you dont run a big risk of running into auto-immunity?
Thats the idea being put forward by some groups that have been studying the connection between HIV-1 infection, ERV expression, and CTL responses to those inappropriately expressed ERVs:
Strong human endogenous retrovirus (HERV)-specific T cell responses are associated with control of HIV-1 in chronic infection
When this group looked for CTLs that responded to ERV ‘flags’, the ranking went:
HIV controllers (no HAART) > HIV on HAART > HIV non-controllers > HIV progressors > Uninfected
The anti-ERV CTLs in the HIV controller group were also ‘broad’– as in, there wasnt just one kind of CTL that could see one kind of flag. There was a population of anti-ERV CTLs that could see lots of variations of the ERV flags. This would be great with HIV, because sometimes it just makes tiny changes to the ‘flag’ via mutation, but ERVs cant do that (they are in your genome, they aint changin), but its still neat.
But, there is a ‘problem’ with studying HIV/AIDS and cytotoxic-T-cells– Its hard to make real connections between CTLs and disease/prognosis, because our conclusions are circular. See, CTLs need CD4+ T-cells. If an infected individual is able to control viral load, they can keep more CD4+ T-cells, and they have more/better CTLs (CD8+ T-cells). People who have more/better CTLs have a chance of controlling HIV better because they can kill infected cells. But which comes first? Chicken or the egg? Viral control or CTLs? So we can make ‘associations’ and ‘correlations’ and see patterns, but we dont know which way it goes. But we can still see patterns in data and learn more, even if we arent certain they are causal:
People with anti-ERV CTLs had lower viral loads
People with anti-ERV CTLS had higher CD4+ T-cell counts
These positive effects were not restricted to people with ‘protective’ MHC alleles
When we have very little to go on for a CTL-based HIV vaccines, Ill take it.