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HIVR4P 2014: Research for Prevention Conference Opens with Real Hope for HIV Vaccine


"There’s only one Berlin Patient still. But by this time next year he will at least be joined by 40-50 Portland monkeys." These were the words of vaccine researcher Louis Picker, summarizing in quotable form why the outlook for the development of an effective HIV vaccine is brighter than it has been for years, in a satellite session in advance of the HIV Research for Prevention conference (R4P) in Cape Town, South Africa.

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Picker was speaking about his research into a vaccine that created a lot of interest at last year’s AIDS Vaccine conference in Barcelona. (The R4P conference results from a merger between the annual AIDS Vaccine conferences and the biennial Microbicides conferences.) Picker said that, by next year, this number of monkeys infected with SIV, the monkey equivalent of HIV, that were also previously given a "replicating vector" vaccine, will have had no detectable virus anywhere in their bodies for more than 70 weeks -- and that probably means not one single infected cell.

The rationale behind Picker’s vaccine is explained in last year’s report, but in brief, it uses SIV genes packaged inside a vector -- a shell of protein derived from the envelope of another virus, in this case cytomegalovirus (CMV), a ubiquitous virus of the herpes family. The vaccine works not by preventing SIV infection, but rather by stimulating such a strong, broad immune reaction to the virus that replication in the infected monkey is suppressed, often to undetectable levels, with infected cells eventually being cleared completely.

This vaccine stimulates the cellular or CD8 branch of the immune system -- the one that kills off infected cells rather than directly targeting viruses. Picker told Aidsmap why CMV is such an ideal candidate for such a vaccine:

"Firstly we know that CMV is unlikely to be dangerous. Nearly everyone has it already. Secondly, despite this, they can be infected with successive strains. Thirdly, it has evolved to generate an immune response in the body that is exactly right -- it’s not one that’s strong enough to get the body to eliminate it (such strong reactions cause the majority of symptoms in viral illnesses), but is just strong enough to stimulate cells to keep turning out new copies of CMV and, in the case of our vaccine, new SIV antigens. It is both harmless yet persistent, which is its strategy for survival and is what you need."

He also seen no reason why it should not work in humans: "We have in fact given monkeys a vaccine based on human CMV and that worked too."

The biggest mystery remains why some monkeys did not respond to the vaccine. But in the latest group of experimental animals, the odds have shifted slightly: whereas in previous groups the success rate was exactly 50%, in the most recent batch to be vaccinated, 16 out of 27 responded (nearly 60%). All but 2 of the monkeys that responded to the vaccine have so far eventually lost every sign of viral infection. There were 2 "breakthrough" infections, though in one case the monkey never developed a detectable blood plasma viral load, just immune signs that it still had viral replication occurring somewhere at a very low level.  

This vaccine, if it works in humans, could also probably deal with re-infection with HIV.

As is well known from cases where people get treatment very early, like the "Mississippi Baby", and from bone marrow transplant recipients, HIV can seem to disappear entirely from the body and the person can become HIV-negative in an antibody test. But once off treatment, the virus has so far always eventually reappeared often after a considerable gap in time -- well over 2 years in the Mississippi case. The one exception is Timothy Ray Brown, the "Berlin Patient," in whom an accidental immune reaction similar to the one produced by Picker’s vaccine may have mopped up residual HIV-infected cells.

Picker illustrated this by showing how SIV apparently disappeared completely from a group of monkeys who were treated with antiretroviral drugs almost immediately after infection. No replicating virus (RNA, as opposed to viral genes, or DNA) was found in them by any method. In 2 monkeys from whom the researchers extracted large number of T-cells (30 million each), they found exactly 1 copy of SIV DNA in 1 monkey and 4 in another. These hard-to-eliminate cells are ones that lie deep in the follicles of the lymph nodes and are not detected by the normal CD8 cells that eliminate virally-infected cells.

Picker then did an experiment that could not be done on a human: he injected these cells into HIV-negative monkeys -- all of whom developed typical SIV infections with high viral loads, showing that SIV and HIV "rebounds" may potentially be generated by possibly only 1 infected cell.

However when he did the same thing to monkeys that had received the CMV vaccine, none of them developed infections.

The CMV vaccine may also be useful in chronic infection. There are 2 ongoing experiments in chronically infected monkeys that have been put on antiretroviral drugs and given the vaccine. These animals will be taken off the drugs in a treatment interruption so see if -- as Picker predicts -- they are able to stay off antiretroviral for a while. Picker told Aidsmap that he does not expect the complete clearance of infection seen in monkeys vaccinated prior to infection, as viral diversity and the number of infected cells is so much greater in chronic infection, but he does expect prolonged treatment breaks to be achievable.

If these experiments go well, then human trials of the CMV vaccine could begin by 2016.



L Picker. Presentation at Help End AIDS Together: Working Toward Vaccine and Cure for HIV/AIDS. Satellite session. HIV Research for Prevention (HIV R4P). Cape Town, South Africa, October 28-31, 2014.