HIV Vaccines– Time to give up?

No.

But if you read last weeks article in The Independent on HIV-1 vaccine research, you might think otherwise.

Here are my answers to The Independents questions. I have the luxury of answering these questions with more than a check mark, but be advised that my answers are tainted with the arrogance of youth, the benefit of hindsight, and obnoxiously high levels of optimism

1. Are you more or less optimistic about the prospects of an HIV vaccine compared to a year ago?

OMG MOAR! This time last year I was so discouraged. This project Im working on for my PhD– it might help lead to an HIV-1 vaccine, and this time last year, I was stuck. But I kept trouble shooting, kept trying this/that/the other, and finally earlier this year I hit several big break-throughs. What Im doing right now is laying the ground work for a logically designed HIV-1 vaccine. I iz happay.

That being said, when I say ‘an HIV-1 vaccine’, I dont mean what you all probably think. I dont mean a traditional vaccine, like polio, where if you get the vaccine, you arent going to get polio except in rare circumstances. I mean a vaccine that can be given to high risk individuals or as a therapy to people already infected. A way to vaccinate against the worst/most transmissable HIVs, so that if you get infected, you wont die from it. I would be happy as a clam if I helped turn HIV into herpes. Sure, it sucks, but it aint gonna kill you.

I do not think a broadly effective HIV-1 vaccine will be possible without some sort of technological revolution.

2. Are you more or less optimistic about the prospects of an HIV vaccine compared to FIVE years ago?

Five years ago, I was a silly little undergrad that thought she wanted to be an MD n/a

3. Do you agree that we now need to change the direction of HIV vaccine research given the failure of clinical trials so far?

YES (again, remember the arrogant kid/hindsight disclaimer!).

Heres the deal. Remember ‘Independence Day’? Remember how when all the alien spaceships came down and blew stuff up, the military was like “OMG SEND IN THE FIGHTER JETS AND THE NUKES OMGOMG!” and they blow up Houston with a nuke and are no better off than they were before?

Thats kinda like what weve done with HIV-1 vaccines.

Imagine youre a scientist in the 1980s and 90s. Youve got this retrovirus that went from a curiosity to a deadly epidemic overnight. OMG. So they tried to make vaccines by throwing everything and everything at HIV-1 (except fighter jets and nukes). But HIV-1 is, evolutionarily, too smart for that. Our old ways of doing things have failed.

*I* think my lab is on to a good new idea that could lead to an HIV-1 vaccine. Not an OMGOMG vaccine. A logical, evolutionarily designed vaccine.

4. Do you agree with the statement that the money being spent on developing an HIV vaccine would be better spent on education and prevention?

Well, the current clinical trials wouldnt have been funded unless they demonstrated, on many, many levels, that they had something that just might work. We shouldnt stop trying ideas that look promising.
That being said, theres a lot of money going into the garbage bin instead of education and prevention, but thats a President Bush issue, not a scientific issue.

5. Do you agree that an HIV vaccine will be developed within the next TEN years?

No. If, tomorrow, I figured out a potential HIV-1 vaccine, it might take ten years to get to the market for Average Joe/Jane. While that might seem distressing, I would rather have a safe friggen vaccine and miss covering people, then accidentally harming people. In the long term, ten years isnt that bad… which is a horrible thing to say to people who have been dealing with the effect of the HIV-1 epidemic for decades…

The uncut answers from scientists are a better read than the actual article. Theyre all being reasonable and quite right: We need to stop screaming OMGOMG and go back to the basic science. Go back to the basic virology. Go back to the basic immunology. Calm down. Do this logically. Do this right.

We might not be able to vaccinate against every possible HIV-1, but we might be able to do other things that can stop/control this virus.

Comments

#1 Felstatsu
April 29, 2008

This is coming from someone who knows a lot more about computer viruses than biological ones.

In computing, there’s mutator viruses, which as the name implies, mutate as they spread. With these computer viruses though, there’s always parts that remain the same, a little identifier tag so the virus doesn’t infect/write over another version of itself at the least, and most also have spawning code that doesn’t change due to the complexity of writing code that changes the program while changing itself. I’m sure it’s already been looked into, but I haven’t heard of any research yet, so have you found any particular section of HIV that remains the same as it evolves?

I realize that genetics and immunology works very differently than computers and it’s entirely possible that there’s no equivalent form of identification tags to it at all, but even if there’s something common to a fair percent of HIV forms it could help cut down on the spread and effects of the virus should a vaccine targeting it be possible to make.
#2 Scott
April 29, 2008

Good answers. I hate it when science is sensationalized all over the place – it undermines the whole point of science; building knowledge from basic principles and observations.
#3 Kevin
April 29, 2008

It’s always good to see another Science blogger obsessed with viruses.

Nature Reviews Microbiology recently posted an interesting article on the challenge of designing an effective HIV vaccine. They do describe an area on the CD4 binding site that is conserved, but actually targeting neutralizing antibodies to that location is quite difficult. Part of the problem is there are incredibly variable regions around the conserved which can prevent epitope binding.

http://www.nature.com/nrmicro/journal/v6/n2/full/nrmicro1819.html
#4 SteveWH
April 29, 2008

ERV – I noticed that you used the word ‘logically’ a couple of times. What exactly do you mean by it? My training is in philosophy, and I think we use the term somewhat differently over on this side of the tracks. Thanks!
#5 Stanton
April 29, 2008

When I took virology, I remember learning about Deltavirus, the pathogen of Hepatitis D, and how it can only infect cells already infected by Betavirus, the pathogen of Hepatitis B. I also remembered learning about a naturally occurring virus that attacks either cancer cells, or certain cells already infected by some other pathogenic virus…

What I’m driving at is, has anyone thought to engineer a satellite virus, akin to Deltavirus, that would infect HIV-infected cells, and either screw up the HIV-replication events or related processes, or kill the infected cell before it can finish replicating HIviruses?

Or is that just a biologist pipe dream akin to Homer Simpson’s dream of Skittlebrau?
#6 ERV
April 29, 2008

Felstatsu– There are definately conserved regions of HIV-1. The problem is, your immune system never sees these conserved regions! They are hidden within the virus, or within the infected cell. Parts of your immune system can see parts of the conserved regions, but not the same parts (hehehe This can be a whole nother post). Youre immune system might be able to see amino acids 5-17 of reverse transcriptase, while mine can only see 13-25. You could, in theory, develop personalized vaccines. Not practical where these vaccines are needed the most. (look up ‘MHC Class I’ and ‘HLA’ for more info)

SteveWH– From my perspective (again, arrogant student), current vaccine strategies arent entirely logical. They are trying everything and anything, instead of using principles of evolution to our advantage to cut an intimidating quasispecies into a manageable group of viruses that are either very pathogenic, or very transmissible, and vaccinating against those. Shooting blindly into the fog after a swamp monster eats one of your comrades is not logical. Waiting until the sun burns off the fog to see, target, and kill the swamp monster is a logical strategy…

Stanton– Could be an idea! Make a parasite for the parasite!
#7 Sven
April 29, 2008

OT: The new rss-feed’s working now.
#8 zer0
April 29, 2008

skittlebrau is the greatest thing evar!
#9 Felstatsu
April 29, 2008

Good to know, well, not particularly good. I’d much rather there be some simpler way to help people than impractical personalized vaccines. Do you think it would be a viable treatment for those who could afford it, or would the difficulty to correctly make it and problems from an incorrect personalization make this a bad idea overall? I’d rather have something that helps everyone, but if there’s an expensive yet viable treatment that could help some people before a catch all treatment can be found I’d like to see some research go in a way to help those people.

I’ll look up the MHC Class I and HLA when I get a chance, probably after work tomorrow, though I would be interested in a post on the interaction between the immune system and the conserved regions as it does sound rather interesting. I knew that different parts of the immune system see and identify invaders in different ways, but I guess I missed the day in bio when differences from person to person were covered or I never got far enough into biology before going into technology to learn that.
#10 Brian
April 29, 2008

I don’t think that HIV vaccines are impossible, but I do think that given the complete lack of neutralizing immunity in any vaccines tested so far, it’s time to stop throwing money at human vaccine trials. CMI responses are not enough, and we know that now. A good CMI in primates doesn’t justify the massive amounts of money that goes into human trials.
#11 Eric Saveau
April 29, 2008

Felstatsu, for this line -

I realize that genetics and immunology works very differently than computers and it’s entirely possible that there’s no equivalent form of identification tags to it at all

I could hug you. I am constantly irritated at the number of people in some computer-related field who say the opposite of what you said above as a way of asserting that evolution is (varying degrees of) false and therefore implying that people like Abby are going about everything all wrong.

Computer technology (on the hardware side) is my field, as well. We have a distressing number of idiots there.
#12 Blake Stacey
April 29, 2008

Off-topic: the Anti-Defamation League has released a statement about Expelled.
#13 TK Kenyon
April 29, 2008

Hi ERV, et al,

A vaccine for HIV will certainly be based on a revolutionary idea. One of the major problems with HIV-vaccine research is that CD4+ cells like monocytes and macrophage express an IgG Fc receptor. Thus, any antibody that sticks to HIV is internalized via the FcR into the CD4+ WBC, and thus the WBC are infected by the tagalong HIV. Even antibodies that are “neutralizing” in a Petri dish *increase* infectivity.

http://www.ncbi.nlm.nih.gov/pubmed/2972065

Thus, I was not surprised when the recent Merck HIV vaccine study went terribly, horribly awry, actually *increasing* the likelihood of infection and earlier death in vaccinated individuals.

http://science4non-majors.blogspot.com/2007/11/recently-merck-pharmaceutical-company.html

Any antibody-stimulating vaccine will have this problem, assuming an IgG response. Passive immunization with F(ab’) fragments might meet with a better result. Additionally, I loooooove Stanton’s Deltavirus/Skittlebrau idea.

And yes, my PhD was in virology. I’m a pathogeek. Sad, n’est pas?

TK Kenyon
Author of CALLOUS: A Novel, ( http://www.amazon.com/gp/product/1601640226 ) a story about free will, neuroscience, fate, Schrodinger’s Cat, and the End of Days.
#14 PalMD
April 29, 2008

Great post! Great to have you here!
#15 Dustin
April 29, 2008

And yes, my PhD was in virology. I’m a pathogeek. Sad, n’est pas?

TK Kenyon
Author of CALLOUS: A Novel, ( http://www.amazon.com/gp/product/1601640226 ) a story about free will, neuroscience, fate, Schrodinger’s Cat, and the End of Days.
Asshole.
#16 PalMD
April 29, 2008

TK, I’m not sure you have a grasp of the whole topic here, but I could be wrong.

Early on in HIV infection there is a VERY vigorous and effective cellular immune response. It isn’t until many years of illness before the immune system loses its ability to fight infections.

Finding a vaccine is not straightforward and is far in the future, but the mechanism you mention does not invalidate the idea (ERV, please correct this non-virologist if i’m wrong.).
#17 BGT
April 29, 2008

TK, plugging your book on this site would be bad form. It reminds others of a certain writer who plugs her rather empty tomes with every post.
#18 ERV
April 29, 2008

LOL! Aw common, its not just ‘buy my book’– its like a sig. But it is cumbersome, so please put the Amazon link as your URL, TR

TR– I have heard of that, but I think it was an initial idea for how HIV-1 infects cells, before they discovered ‘exactly’ how HIV was infecting cells (they didnt know about co-receptors, CXCR4 and CCR5 back then). It turns out the co-receptors were causing the macrophage/T-cell differences in tropism that they were seeing, not the Fc receptors on macrophages.

But my experiments are done in a variety of cell types, with and without Abs, so if there is a detrimental effect of HIV antibodies with macrophages, Ill see it
#19 ERV
April 29, 2008

Dammit, TK, not TR (Im used to TR Gregory, sorry).
#20 Fleming
April 30, 2008

The quest for an HIV vaccine is an utter failure. All scientists who have been part of this inept quest should really be fired.
#21 Eric Saveau
April 30, 2008

The quest for an HIV vaccine is an utter failure. All scientists who have been part of this inept quest should really be fired.

And replaced with whom? Or are you saying that no one should even make the attempt?
#22 Felstatsu
April 30, 2008

Eric Saveau– Wow, didn’t expect to make anyone that happy with just one line. I’m one of the odd ones out for the technology fields, when I got to college I had no idea what I wanted to do and only a few things I knew I didn’t want to do. I think getting the basics in a whole lot of fields can benefit everyone since it tends to show you how little you know. Glad I made you happy, I’m here to learn since recently I’ve started getting seriously interested in biology and viruses again, making someone’s day is icing on the cake.

Flemming– So Thomas Edison saying “I have not failed. I’ve just found 10,000 ways that won’t work.” is something you don’t agree with I take it. We rarely get anything but the simplest of solutions on the first try, something as complex as an HIV vaccine could take thousands of tries before something works. Without trying we’ll never know if something works and by failing we learn as much, if not more, than when we get it right. Also, to echo Eric above me, before you start saying something like you have, come up with a better way to find a solution to HIV or give a reason why we shouldn’t even try.
#23 bayman
April 30, 2008

Stanton:

It is a good idea.
Some work has been done in fact:

http://www.ncbi.nlm.nih.gov/pubmed/9298897?ordinalpos=41&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Lots of great ideas out there…so little time and money to test in humans. This is the bottleneck.
#24 arthritistreatmentguy
April 30, 2008

another problem with vaccination is that HIV mutates very very fast.
#25 Steven
April 30, 2008

Give up trying to make vaccines? Stupid question. Obviously no.
#26 JustaTech
May 1, 2008

ERV, so you know, my lab is coming up with a new way to test HIV vaccines in mice. (Yes, I know, it’s impossible. That’s why we’re doing it.) It’s not a protection test, but an immunogenicity test. Our hope is that this will eliminate unsuccessful vaccines before they go to primate trials.

And to anyone who says that we’re incompetent and should be fired, I really don’t think you understand 1) science in general, particularly biology and 2) HIV in particular. Understanding HIV has been like finding the headwater of the Nile. On paper, it’s simple. In practice there are waterfalls, crocodiles, and malaria.