April 10, 2012
Toward a Cure: The Potential of Therapeutic Vaccines
by Tim Horn
While gene therapies that render the immune system impervious to HIV and drugs that potentially purge the virus from resting CD4 cells continue to be watched closely by AIDS cure researchers and advocates, therapeutic vaccines may serve an important supporting role in these efforts, according to a commentary published by activist Richard Jefferys in the Spring 2012 TAGline newsletter.
“After a period in which enthusiasm regarding the prospects for therapeutic vaccines waned,” Jefferys writes, “the recent resurgence in interest in research aiming to cure HIV infection has offered new reasons to pursue their development.”
Notable therapeutic vaccines for the virus use HIV particles, sometimes paired with other viruses, or largely intact HIV, to jumpstart the immune system’s perceived ability to control viral replication in the body. Such vaccines have been conceptualized and explored since the mid-1980s. “But the first efforts toward this goal quickly mired therapeutic vaccine research in controversy,” Jefferys writes, “casting an initial pall across the field that was compounded by the failure of any candidate to show significant efficacy.”
Jefferys explains that therapeutic vaccines are now in their third—and potentially most critical—era of development, noting that the first two eras didn’t pan out for important reasons.
In the first era, dating back to the 1980s and early 1990s, therapeutic vaccine candidates of the day faced significant hurdles that were unknown at the time. For example, it was once assumed that HIV is mostly dormant during the asymptomatic and untreated years of infection and that CD4 cells lacked the ability to respond to HIV. Subesequent findings proving these hypotheses wrong, Jefferys writes, "seriously called into question the idea that adding more HIV antigens into the mix via therapeutic vaccination—when the virus itself was failing to induce protective immunity—would be beneficial."
In the second era, with viral load technology and combination antiretroviral therapy (ART) widely available, therapeutic vaccination plans evolved. One approach was to bolster the immune response to HIV while study volunteers were keeping their viral loads undetectable using available ARVs, followed by treatment interruptions to test the immune system’s ability to control HIV replication in the absence of therapy.
“Once again,” Jefferys explains, “scientific advances served to undermine the rationale behind these studies. Specifically, the idea that [ART] could be safely interrupted as long as CD4 T-cell counts were maintained was shown to be erroneous by the sobering results of the Strategic Management of Antiretroviral Therapy (SMART) trial. SMART had the specific goal of assessing whether intermittent, CD4-guided ART could be as effective as continuous ART, but the trial had to be stopped early because individuals in the intermittent arm experienced a doubling in risk of illness and death. Analyses demonstrated that these events were associated with inflammation resulting from unsuppressed viral load, prompting additional investigations into the link between inflammatory markers, uncontrolled HIV replication and health outcomes.”
In the current third era, as Jefferys makes clear, the various shortcomings of therapeutic vaccine research completed thus far mean that the bar has been raised. “The key question has become, Is it possible for a therapeutic vaccine to generate HIV-specific immune responses capable of completely containing viral replication when ART is interrupted? This may seem like a dauntingly high hurdle given results to date, but it dovetails with emerging research that has recently resurrected therapeutic HIV vaccines for the third time. This research is in pursuit of the ultimate goal: a cure for HIV infection.”
One potential avenue of research: using therapeutic vaccines to bolster the CD8-cell response that may be necessary to kill CD4 cells that have had their dormant HIV awakened using HDAC inhibitors or other reservoir-purging drugs. One paper reviewed by Jefferys, presented at the recent 19th Conference on Retroviruses and Opportunistic Infections in Seattle, “presented compelling evidence that simply rousing HIV is not sufficient; CD8 T-cells are needed to deliver the coup de grace and kill the infected cells.”
Jefferys concludes: “Despite the history of controversy and uncertainty, the ascendancy of cure research has provided a strong and scientifically sound rationale for further studies of therapeutic HIV vaccines. The goals are now far clearer: to achieve containment of HIV replication and prevention of disease in the absence of ongoing treatment (now described as a ‘functional cure’), or complete elimination of the virus (a ‘sterilizing cure’).”
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comments 1 - 12 (of 12 total)
Isaac, Kampala, 2012-11-21 10:23:23
I am impressed by the update information on Therapeutic HIV vaccine. I appreciate all efforts directed to the fight of this pandemic. send me more info from time to time. Thanx
keith, EU, 2012-07-01 19:14:45
In relation to vaccines
I have faith in the Vacc 4x and Vacc 5 it maybe wont be a "cure" but a replacement for HAART that will make HIV more manageable like herpes.
In relation to cure I have hope in these cord blood tests been done if they work HIV IS CURABLE and it wont take 10 yrs we will now if it works by christmas
jimmok, DC, 2012-06-02 22:31:09
brothers and sisters afflicted with hiv..all these news are good but we will be able to see the benifits of these only after a decade or so if there is ever going to be one...but i i have doubts.i know that i will never reap the benefits but hope that all the people around the world would be able.i also pray that a cure comes in the lifetime of who ever is reading this.ty
BASHA, Uganda, 2012-04-19 01:25:50
I know that researchers are working tireless to find a cure and a lot has been said about working towards a cure, but the question is when eish our brothers and sisters are dying ,to the almighty HELP THE RESEARCHERS ON THE FIELD TO TACKLE THIS KILLER. AMEN
BettyForACure, , 2012-04-15 09:52:12
It's going to HAPPEN everyone! May not be for another few years, but by faith, persistent and advocacy to find the cure. Too much is emerging in the field to ignore the real possibility of a 'functional cure' being discovered. I do however, believe it will be treated much like cancer. It's important to keep our bodies in the best shape possible (take your meds) to receive such treatment! AND to all the nay sayers who believe there is some conspiracy I cant wait to see you all eat your words!
Brian, Beantown, 2012-04-13 08:31:18
Apologies for my thinking I was censored-I realize now there are 2 articles on vaccines--sorry to your moderator-who has been very forward in letting most posts go through-whether we are jaded or misguided and even paranoid it is great to have a forum where we can share from our collective years of experience. Vaccines IMHO have languished because they don't offer big profit motives that pharma's do, and it sure seems like the next drug in pipeline conveniently appears when patent is up-shame!
Brian, Beantown, 2012-04-13 08:04:10
There are obviously many dedicated researchers out there trying to find a "cure"-however, vaccine research-as told to me in 94-offers the best hope for a "cure" and since then it has fallen on its sword time and time again. It is hard not to be cynical when one sees the retail price Medicare would pay if one went outside private health insurance-for me 60,000 a year..the same meds would cost an African (after waiting 10 awful years) about 1000 dollars-virtue is its own reward-blood money is not.
john, breslau, 2012-04-13 04:29:50
David Margolis the University of North Carolina at Chapel Hill
Mar 9, 2012
“What people want to know is when can someone go to a doctor and be handed a pill and be cured,” Margolis said by phone. “That’s decades away. Think of it more in terms of curing cancer. I think in 10 years someone with HIV infection could go to a specialist and get a complicated treatment and have some likelihood of a prolonged remission of their HIV.”
ryan, philippines, 2012-04-12 06:14:11
Hope cure will be served fast. People are dying.. Any clinical trial in the Philippines?
Eric Chikukwa, Harare, 2012-04-12 04:29:06
I applaud the players at various levels who are researching for a cure. Those of us at working at community level feel strengthened and hopeful when we read such news. whenever we read
lolo, denmark sc, 2012-04-10 16:03:52
i would like to be in the trail i been livein wit hiv for 10 years and not on meds
wanting to try, seattle, 2012-04-10 15:05:30
comments 1 - 12 (of 12 total)
When will this be offered for trial? As I am living with this disease and have been for 4 years now...I'm eager to do trial therapies. I am on atripla, my counts are great, and my doc says I'm undectable. Please, someome advise how I can become a test candidate.
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