More baby steps in AIDS research

As a follow-up on the AIDS vaccine post, here is an upcoming article from Science about the identification of antibodies active against the HIV virus, identified in the blood of an african donor.

There is an ongoing effort to isolate antibodies that neutralize the HIV virus from people infected with the virus. One of the reoccurring issues with these neutralizing antibodies is that the ones identified so far are very specific against the strain which infected that particular individual, but don't do much for somebody infected with a different strain (or maybe not even a mutated form of the same strain).

Antibodies in general tend to be very, very selective against a particular target, which is desirable for antibody-based medicines, since it reduces the risk for unwanted off-target activity, but not so desirable if you are trying to target something like HIV, where you are dealing with multiple, constantly evolving strains.

Also, with antibodies you mostly observe is that the less selective the antibody, the less potent it tends to be.

Having said that, what makes this article noteworthy is the fact that now for the first time they succeeded in isolating "broad and potent neutralizing antibodies". The two antibodies identified showed potency against 127 and 119 different strains of HIV, out of a total of 162 strains they were tested against.

So this looks very promising and might open the door for antibody-based treatments for people infected with HIV.

To follow-up on the vaccine story: the problem with the AIDS vaccine is that it showed only partial efficacy. Using the knowledge from these antibodies would be just what is needed to come up with a better vaccine, i.e. one that is potent against a broad range of HIV strains.
But the details in the article show how difficult it is going to be to use this as the basis for an AIDS vaccine:

When the team looked into what made these antibodies so potent against such a broad array of HIV strains, they found that the antibodies did not work at all when exposed to isolated proteins from the surface of the HIV virus. They only worked against a trimer that is formed by three proteins on the surface of the HIV virus and they bind to a specific part of the overall surface formed by these 3 proteins.

This is going to make it hard to use these findings for an AIDS vaccine, since you can't tell the human body "Go make exactly this antibody". You can only take something you want the immune system to react to, put it into a vaccine, and let the immune system come up with a way to deal with this.

So even if you manage to put these 3 proteins that were identified (or pieces of these proteins) into a vaccine, there is no telling exactly which part of the overall protein surface the antibodies produced by the immune system are going to bind to.
So when somebody gets the vaccine, the immune system might produce antibodies that are very selective, binding to some other part of the protein surface, and not have the broad spectrum of potency that is needed to fight an HIV infection.

In the article some initial work was already done to identify exactly where and how the antibodies bind to that trimer, let's hope that this can be used to synthesize a protein fragment that would trick the immune system into producing the right antibodies.

... and also hope HIV is not going to quickly mutate its way around this, as it has done before.

Ref.:

Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW, Protocol G Principal Investigators, Miiro G, Serwanga J, Pozniak A, McPhee D, Manigart O, Mwananyanda L, Karita E, Inwoley A, Jaoko W, Dehovitz J, Bekker LG, Pitisuttithum P, Paris R, Allen S, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, & Burton DR (2009). Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target. Science (New York, N.Y.) PMID: 19729618

Towards an AIDS vaccine, once more

There is some hopeful news that an AIDS vaccine might be possible.

There have been multiple trials with AIDS vaccines in the past, all of which have failed, but now for the first time there is some clinical data that shows that infection rates were in fact lowered by the vaccination. Only by a third, though, so there is still a long way to go, but it is a step in the right direction.

Why, you ask, is an AIDS vaccine so hard to develop?

The reason is that almost all vaccines work on diseases that the human body can successfully fight on its own, mostly. Take for example smallpox, where about two thirds of the infected did recover from it before vaccines against it were developed. So all the vaccine needs to do is to prepare and boost the immune response ahead of time. This is how most vaccines work.

Chronic diseases on the other hand have managed to develop strategies to outsmart the human immune system. No matter how hard the immune system tries, for the vast majority of people the immune system can not clear the infection. So simply boosting and preparing the immune system through a vaccine does not work here, since there is no adequate immune response in the first place.

This is the reason why for this AIDS vaccine a different strategy was used. The vaccination consists of two vaccines, each of which works through a different mechanism. One of the two had been tested before and was found to not work well enough on its own.

The downside of this study is that the vaccines did specifically target HIV strains circulating in Thailand, where the study was performed, and even then only partial protection was achieved.

So maybe as for the AIDS drugs, the way forward for an AIDS vaccine is to have cocktails of different vaccines that complement each other.

If (big if) these initial results hold up.