On HIV vaccines

On a somewhat related note, any comments on the Texas decision not to do manditory vaccines? Some of the information out is conflicting. And you've already talked about many of these issues. One of the statistics is that only 18% of vaccinated girls would be protected (though this is almost certainly wrong). But that would still be over 300,000 protected women. But wouldn't it be more? After all, it would decrease the transmission of the virus.

So, clinical trials started today would show real statistics in 20 years. Would today's vaccine still likely be relevant in 20 years?

Thanks for the link.

Hmmmpht.

Only two comments? Would have thought mention of HIV and vaccines in the same post title would have brought out the HIV-denialists and the anti-vaxers at the same time.

Tara,

FYI, there was a useful commentary by the authors of the NEJM paper in the San Francsico Chronicle a few days ago:

What can we expect from the first AIDS vaccine?
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/05/18/EDGKOP3EFP1…

Margaret I. Johnston, Anthony S. Fauci

Friday, May 18, 2007

Significant progress has been made toward the goal of developing a safe and effective HIV vaccine, although many challenges remain. We now know more about HIV, the virus that causes AIDS, and have more promising vaccines in development than at any other time in the history of the HIV/AIDS pandemic. While a vaccine that prevents HIV infection has always been and still remains the aim of HIV vaccine research efforts, years of research have led us to expand our thinking about how an HIV vaccine might work. Specifically, development of a vaccine that does not prevent infection completely but that slows the progression of disease in people who get infected despite vaccination could still serve as a positive intermediate step in the search for a safe and effective AIDS vaccine that completely prevents infection.

Most "classical" vaccines against viral diseases -- seasonal influenza, polio, and rabies -- stimulate antibodies (protective proteins) that control the virus, prevent disease and ultimately rid the virus from the body. However, inducing such effective antibodies against HIV is an extraordinary challenge because the virus has multiple ways of evading the body's immune defenses.

HIV rapidly mutates; and these variants of HIV change continually, and an infected person's immune system invariably cannot keep up with all of them. In addition, within days of infection, HIV begins to destroy critical immune cells that would normally protect against the virus; this attack on the body's defenses is relatively unique. Finally, HIV inserts itself into the DNA of human cells where it can remain undetected by the immune system. Even with extended drug therapy that reduces virus in the blood to undetectable levels, HIV is not eradicated from the body. These challenges have made it extremely difficult to design a vaccine that prevents an infection from establishing itself in the body.

In the face of these enormous scientific challenges, will a vaccine that can help control the AIDS pandemic ever become a reality? A "non-classical" approach to HIV vaccine development is evolving. Research in animal models of AIDS has demonstrated that vaccines that stimulate immune cells, called T cells, which do not attack the virus directly, but can recognize and kill HIV-infected cells, might be beneficial even if the vaccine does not completely prevent HIV infection. In animal models of HIV disease, vaccines that induce these types of T cells and that were given before the animals were exposed to virus blunted the magnitude of the initial infection, preserved immune-fighting cells, and resulted in a longer disease-free period.

Thus, a non-classical HIV vaccine given before an individual is exposed to the virus may not prevent initial infection or eliminate HIV or prevent disease entirely, but it might induce T cells that control HIV, contain the virus at low levels, and substantially delay the need to start drug therapy. In addition, because the efficiency of transmission of HIV from one person to another is directly related to the level of virus in the transmitting partner, restricting the virus to very low levels could lessen or even halt person-to-person HIV transmission. A vaccine that achieved these objectives could have a huge individual and public health benefit in mitigating the HIV epidemic.

In previous clinical trials, several experimental HIV vaccines have induced strong T-cell responses, yet many years of expanded clinical trials will be required to test the potential utility of these non-classical vaccines. Two such large, international trials have already started and a third may be initiated later this year, each requiring thousands of volunteers.

We must move cautiously along this uncharted path. If such a non-classical vaccine proves to be effective in clinical trials, the vaccine would need to be delivered as part of a multifaceted, comprehensive HIV prevention program so that recipients minimize or eliminate behaviors that expose them to HIV. Otherwise, any beneficial effect of the vaccine could be eliminated.

An effective HIV vaccine is our best hope of preventing the approximately 14,000 new HIV infections that occur daily worldwide. Research to design a classical vaccine that prevents HIV infection must continue. Given the urgent need to identify improved HIV prevention tools, however, we must pursue all promising avenues, including non-classical vaccines.

Today, HIV Vaccine Awareness Day, we also want to thank all the past, current and future community volunteers and researchers who are working to make a successful preventive HIV vaccine a reality. Their combined efforts and long-term commitment are critical if we are to be the generation that stops the relentless spread of AIDS (www.bethegeneration.org).

Margaret I. Johnston, Ph.D., is director of the Vaccine Research Program in the Division of AIDS at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Anthony S. Fauci, M.D., is director of the National Institute of Allergy and Infectious Diseases.

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If one is HIV-Positive, which in theory already has antibodies to HIV, then that person should already be protected against the virus. It amazes me how highly educated persons do not look into the sexually transmitted disease statistics provided by the CDC. With up to several millions occurring each year in the U.S. and supposedly having an STD will increase the chance of contracting HIV, then why have the HIV numbers stayed around 40,000 all of these years and stayed mainly in the male population? If HIV was truly transmitted by sex, then the HIV statistics should reflect this in the race, sex, age group and the section of the country, which has been proven to have the most std's. It does not.

If someone develops a vaccine for HIV and it is given to HIV-Negatives for prevention, this will not stop AIDS, which is due to health issues and habits of the person but it will make a ton of money for someone.

Dr. Andy mantious brought up a great point. If there ever is a successful vaccine, everyone who gets it will test positive! So they will be in the same boat as people that were infected already in some ways. Something doesnt add up here.

Noreen,
you say "If one is HIV-Positive, which in theory already has antibodies to HIV, then that person should already be protected against the virus."

I don't know how many times you have been told this but I'll say it once again - this is nonsense! HIV antibodies are not protective. The immune response to different pathogens differs - so infections such as syphilis, for example, can generate antibodies but no protection against re-infection. For chronic latent viral infections, antibodies can be detected but do not prevent reactivation or ongoing infection from occurring.

Check this for yourself up for viruses such as CMV, EBV, VZV, HSV, HCV etc, as well as HIV. Antibodies indicate prior infection, not protection. Duesberg still denies this fact, but even someone like yourself without a science background is capable of confirm the truth of these statements with a little web browsing.

In terms of vaccine protection vs HIV, you may not expect a vaccine that induces simple neutralising antibodies to be protective. This principle operates for other infections too, besides HIV. You really need a good specific T cell response rather than a poor B cell response.

HIV vaccines are of 2 types - the article above explains how boosting someones T cell responses in someone who already has HIV can indirectly help control viral replication. This is a stategy that has worked well in animal models of HIV and trials are ongoing in humans.

Your persistent faith in the idea that HIV does not cause immunodeficiency and AIDS is admirable, in the face of all the evidence to the contrary, but may ultimately cost you dearly.

With respect, you need to wise up on STD epidemiology, too. Not all STIs are the same. Many are largely confined to certain population groups because of sociodemographic factors and biological constraints regarding the pathogens and how they are transmitted (eg which parts of the genitals are exposed to the pathogen and in what way - does it have to be mucosa that is rich in dendritic cells, or will intact skin do?).

If you look at STI patterns accross the US you will see great discrepancies in prevalence and incidence of infections such as syphilis, HPV, chlamydia etc. Perhaps you think (like Duesberg does) that syphilis is not an STI, because in whites males it is 10x more common than in females, or because it is 3x commoner in the North East US than the South?

HIV prevalence within the population at risk of other STIs is relevant. If there is no HIV within an isolated subgroup of promiscuous individuals, HIV infection obviously will not occur or spread until it is introduced from outside. We have seen this often with small groups of gay men who frequent the same saunas for instance. This is also true for drug users. In Scotland, there were several areas of cities like Dundee and Edinburgh where needle sharing was rife, but the nature of drug use was for people to be faithful within their own group/subculture. In some groups where HIV was introduced it affected 40-50% of users. However, there were some groups in different parts of the city who escaped HIV and have very low prevalence rates because they never shared outside their own group. In Glasgow, part of the drug using culture was to use citric acid to dissolve the heroin, something that was felt to have contributed to a lower HIV rate in this city because it can inactivate HIV. You see, one cannot jump to conclusions about pathogens with complex transmission routes in the way you do unless you know a lot more of what is happening with the local epidemiology.

You will also find that only some STIs will increase the chance of HIV infection. HIV quite hard to catch really, but if there are ulcerated areas of the genitals that will be exposed to virus then transmission is more likely to happen since the protective barrier is compromised. Yet some infections will not increase the risk because they do not sufficiently alter the biological barriers (eg HPV, chlamydia, GC). Yet HSV or syph will, and can facilitate transmission.

BTW, welcome to a "thinking" science blog. You have spent too long reading Hank Barnes and other denialist blogs where any dissent with their view is censored and adhominems are rife. Here you can discuss freely, and learn to think for yourself oncemore.

When a public piece begins like the one by Johnson and Fauci posted above by 'Manny' one had better take the opportunity to go to the toilet or do the gardening or something, because that's a sure sign one is about to be fed braindead infoganda:

Significant progress has been made toward the goal of developing a safe and effective HIV vaccine, although many challenges remain. We now know more about HIV, the virus that causes AIDS, and have more promising vaccines in development than at any other time in the history of the HIV/AIDS pandemic

Anthony Fauci says he uses his sister as a barometer of lay people opinion when addressing the issues of HIV/AIDS publicly. If that is so, his sister must be vegetarian, because this is one beefless burger.

When, for example, would any AIDS Inc. official not claim "significant progress" has been made in HIV science?

How about, "sorry fellas no progress the last couple of decades, your tax money was wasted" signed Tony?
That'll be the day Bush says sorry for invading Iraq.

"We now know more about HIV, the virus that causes AIDS, and have more promising vaccines in development than at any other time in the history of the HIV/AIDS pandemic"

And is there any other time in history where this statement wouldn't be equally true? Or does scientific knowledge about HIV increase and decrease like co-factor influenced CD4 counts? Vintage Fauci waffle.

Here's how Fauci explains the science to his sister:

HIV inserts itself into the DNA of human cells where it can remain undetected by the immune system

Grim prospect, and yet it would seem something detects HIV infected cells at some stage after all:

Research in animal models of AIDS has demonstrated that vaccines that stimulate immune cells, called T cells, which do not attack the virus directly, but can recognize and kill HIV-infected cells, might be beneficial even if the vaccine does not completely prevent HIV infection.

So, research in those perfect animal models of AIDS where most get sick within weeks or months as a direct result of primary infection shows that a T-cell boost "might" be able to slow down progression towards AIDS in humans a decade or two down the road because it "blunts initial infection". What would that amount to one wonders, 20 years instead of 15? Maybe Prof. Jaroslaw Stark could redeem himself by doing the mathematic modelling now that he has been set straight on "the data". http://scienceblogs.com/aetiology/2007/06/hivaids_denial_featured_in_sc…

But why the sudden enthusiasm for out of the box thinking? well, it seems if funding can be diverted towards one's own pet projects it won't hurt diluting the perennial cup of optimism and excitement of scientific discovery with a discrete drop of scepticism. Johnson and Fauci summarizes the "significant progress" towards a classical HIV neutralizing antibody vaccine thus:

In the face of these enormous scientific challenges, will a vaccine that can help control the AIDS pandemic ever become a reality?

We hope so Drs. Johnson and Fauci, we hope so, because it hasn't been cheap so far.

Fortunately the real Pope doesn't share this sudden pessimism. Gallo's faith and - what amounts to the same - ambition are unshakable:

I am of the school with HIV - not everybody is in this school - but because it's a virus that we call a retrovirus, they integrate their genes in the target cell DNA in our chromosomes, so the cell that gets infected is infected forever, and quite rapidly. Moreover, because it's in the DNA of the cell, when the cell divides and becomes two cells, those genes are transmitted to the daughter cell as well so the individual is infected forever. Thus, I believe we have to block at the gate where the virus comes into the cells, and I believe we have to come close to sterilising immunity which means no cell gets infected - maybe not absolute, but darn close to it. To my knowledge, no-one has ever achieved any microbe sterilising immunity (...)We knew to do that right at the beginning of the field in 1984 when we really understood this virus; we knew we would probably have to achieve that so how do you do that? How do you make antibodies that block? We call those neutralizin antibodies. You have to do it with the envelope proteins.
http://garlan.rethinkingaids.info/Cases/Parenzee/Gallo-Transcript.html

Ah yes, the scientific spirit of healthy ambition, healthy optimism/pessimism and healthy competition for funding, fame and the Prize.