A call to Bill & Melinda

Gates FoundationI received a comment from “Phil” today that led me to respond, as follows.  After writing my response, this looked more like a blog post than a comment…..and so here it is.

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Phil wrote:

“Hi Bill I look up herpes cures, vaccines and research most days. I’ve also been reading a lot about hiv cures. Seeing as a lot more money seems to be spent on that over herpes could it ever help finding a cure for herpes if they did find a cure for hiv? Are they similar at all ie would a hiv cure mean it should be easy to find a herpes cure? Also I’ve read recently they may have found a way of starving the HIV virus from the sugars etc it needs to live. Could this also be done for herpes? Surly the virus needs certain things to live? Is there any way to starve the herpes virus so it would die off? Thanks Phil”

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I respond……Hi Phil,

I think there is some merit to a concept you touch upon in your comment. Specifically, you asked, “Are they similar at all ie would a HIV cure mean it should be easy to find a herpes cures?”

I would suggest that a more scientifically accurate way to look at this question is to flip it around and re-state it as follows: “Is the process of vaccinating against a diversity of infectious diseases similar enough in principle to curing HSV-2 genital herpes with an effective vaccine that we might learn something useful about how to prevent other infectious diseases?

The idea of subunit vaccines was held up as a panacea in the late 1970s that would cure all infectious diseases moving forward.   The tools to manipulate genes underwent a revolution in the 1970s (the recombinant DNA revolution), and one of the ideas that was envisioned was removing small pieces of genetic code from microbes and using these pieces of recombinant DNA to encode a single protein antigen, or subunit, from the infectious agent such that an uber-safe vaccine could be created.  This was the birth of the “subunit vaccine” hypothesis.  As often happens in science, the actual product did not live up to the spirit of the idea that was promised…..and hence, we still lack a real cure for HIV/AIDS, HSV-2, malaria, and tuberculosis.  Unfortunately, with the passing of two scientific generations, most of my scientific peers were taught in the 1990s and 2000s to assume that subunit vaccines may be used to cure any infectious disease.  Hence, a majority of scientists have lost sight of the fact that the “subunit vaccine concept” is a hypothesis, and the data collected to date raise serious questions about the tacit assumption that subunit vaccines achieve the same end result as the live vaccines that preceded them.  This prevailing belief lingers despite a growing mountain of evidence to the contrary.

If I could get the ear of Bill & Melinda Gates, I would tell them that their Foundation is a wonderfully inspiring idea and their hearts are so clearly in the right place. However, the best way they could invest their money in the future would be to support the deployment of a safe and effective live-attenuated HSV-2 vaccine. Honestly, one of the least important implications of my HSV-2 vaccine work is the ability to cure herpes. Don’t get me wrong…..this is a very important goal and I am pushing for it every day. However, the real importance of my lab’s live-attenuated HSV-2 vaccine is that it functions as a “model organism” of sorts to explore what is so very, very wrong with current thinking about vaccines. If all of the immunologists’ ideas about subunit vaccines were correct, then AIDS, herpes, TB, and malaria would have all started becoming vaccine-preventable diseases in the early 2000s. However, the data is in, and the substance of subunit vaccines simply falls short of the mark. In 2015, we continue to invest 99% of our vaccine research money into new permutations of the same, tired subunit vaccine concept that has been failing for 30 years.

In contrast, live-attenuated vaccines to prevent HSV-2, HIV, malaria, and TB have gotten short shrift, and so these radically different vaccine approaches (which are potentially hundreds of times more effective) lay dormant and understudied despite their potential to start preventing human disease today. Scientifically, this is a travesty and represents a 21st century equivalent of allowing the mainstream of “leading philosophers” to not let Christopher Columbus sail west from Portugal because they “know the world is flat” and his ship will fall off the edge of the Earth. The thought process that holds back inquiry into live-attenuated vaccines that could be used to safely prevent HSV-2, HIV, malaria, and TB amounts to little more than established vaccine scientists who are over-invested in subunit vaccines not wanting to lose control of their fiefdom of power, even when millions of people’s lives hang in the balance depending on the outcome of the next HIV, malaria, or TB vaccine trial.

Bill and Melinda, if you are listening, the single-most powerful thing you could do with your Foundation is give hope to the tens of millions who suffer with HSV-2 genital herpes that they will be the last generation to suffer with this disease that strips people of their normalcy and hope for a better future. Support a program to test the world’s first live-attenuated HSV-2 vaccine in human clinical trials!!! At the same time, the advancement of this model rationally-engineered live vaccine (RELV) could help expose the lies and folly that underlie claims that “live-attenuated vaccines are too dangerous to study in the human population.” Live vaccines that were randomly isolated (and thus not particularly safe) between 1798 and 1974 have saved millions of human lives from death and disease (e.g., MMR, VZV, polio, smallpox, etc). Now that we can genetically engineer microbes in a very precise manner to be “rationally attenuated” (i.e., we understand why the genetic change attenuates the microbe), this should make RELVs far safer relative than the randomly-isolated live vaccines we currently use to safely protect millions of children around the world from infectious disease (MMR, VZV, oral polio).

In June 2015 alone, more than 150,000 people will die of AIDS, TB, and malaria. How much longer can we afford to not study RELV-based vaccines that offer a new and unexplored hope to end these and other infectious diseases? Subunit vaccines have failed in trial after trial for decades. It is time to try a different approach that is potentially hundreds of times more effective.

I am all about changing the world for the better, and the deployment of the world’s first rationally-engineered live vaccine (RELV) based on a HSV-2 ICP0¯ mutant represents a major step in that direction. Bill and Melinda, you can help make that happen and I assure you that this would be a wise use of your Foundation resources, as you would both (1) cure a chronic disease that destroys millions of lives (i.e., HSV-2 genital herpes), and (2) simultaneously establish a precedent that raises the important question, “Is the testing of RELVs to prevent HIV, TB, and malaria really ‘too dangerous’ to consider?” I would suggest that the real danger here lies in continuing the status quo, and only testing “safer” subunit vaccines which are unlikely to stop millions more from suffering and/or dying from what should be vaccine-preventable diseases.

Using a RELV to successfully prevent HSV-2 genital herpes represents a potential watershed moment in infectious disease, which could highlight a new approach to solve infectious disease problems that have proven recalcitrant to subunit vaccines.  Bill & Melinda, I am happy to help with the science.  It would be great if you could assist with the capital so that we can put the ball across this most important of goal lines.

– Bill H.