May 16, 2014 |
For those of you who follow this blog with some regularity, I thought a quick post was in order to acknowledge that this blog site is approaching its first anniversary; the first blog post was made on June 15, 2013. By June 14, 2014, the Herpesvaccine Blog will have been visited over 116,000 times. Thank you one and all for your support.
From my perspective, perhaps the most notable / important utility of the Herpesvaccine blog has been in providing me with an initial outlet to help identify gaps in my own thinking and in my field of study that are important, but which are often not discussed in a clear and transparent manner in the scientific literature.
A case in point is my first full-length post on this blog entitled “Why don’t we have a HSV-2 vaccine yet?” I opened this post with the following statements:
“The true definition of madness is repeating the same action, over and over, hoping for a different result.” – Albert Einstein
A common problem in science is that the natural world does not always conform to our initial expectations about how things “should work.” In a nutshell, this is the primary problem that has plagued herpes simplex virus 2 (HSV-2) vaccine research for the past 40 years. I elaborate below.
In this initial post I made a case that the primary reason we still lack an effective HSV-2 vaccine in the clinics is that, in essence, we have only seriously considered a single approach; namely, vaccines based on HSV-2’s glycoprotein D protein plus an adjuvant. In contrast, a live-attenuated (replication-competent) HSV-2 vaccine has never been tested despite the success and safety of similar live-attenuated vaccines used to prevent smallpox, yellow fever, polio, mumps, measles, rubella, chickenpox, shingles, and rotavirus-induced diarrhea in small children.
Fast forward nearly a year. My laboratory has just published a full-length, peer-reviewed article that makes this same argument, but in a much more complete manner and which cites over 200 published studies, hence offering the reader with my opinion on the important question of why we still lack a HSV-2 vaccine, but against the backdrop of the past 40 years of research and clinical literature on the topic.
The link to this June 2014 review of the status of HSV-2 vaccine research may be found here: http://informahealthcare.com/doi/abs/10.1586/14760584.2014.910121
I close with the following text from the Prologue of the review, which summarizes the intended purpose of this new review of the HSV-2 vaccine research literature:
“Herpes simplex virus 2 (HSV-2) vaccine reviews often provide an overview of which vaccine approaches have been considered in recent years [1,2]. The current review focuses on what I believe is a more pressing question: Why do promising HSV-2 vaccines keep failing in clinical trials [3–9]? What doctors and the general public desire is a HSV-2 vaccine that works. What scientists desire is a better understanding of how to separate the wheat from the chaff when it comes to HSV-2 vaccines. The intention of this review is to consider such matters.
I hope to make plain that ‘antigenic breadth’ is a critical concept in HSV-2 vaccine efficacy, but has slipped under scientists’ radars for too long. Although vaccine scientists have been testing HSV-2 vaccines for three decades [10,11], the spread of HSV-2 genital herpes has not been slowed. Millions of our children will suffer the same fate unless we advance an effective HSV-2 vaccine into clinical trials posthaste. The key questions are, ‘Is HSV-2 genital herpes a vaccine-preventable disease?,’ and if so then ‘Which HSV-2 vaccine approaches are most likely to achieve this goal?’ Against this backdrop, I discuss what I believe has gone awry with past HSV-2 vaccine strategies and consider what we might do differently in the future to improve our odds of success.
It is my sincere hope that this review may help remind one or more academic scientists and/or vaccine industry leaders that, for better or worse, we are the individuals responsible for choosing which HSV-2 vaccine approaches will, or will not, be explored in the future. The past decade of HSV-2 vaccine research has been fraught with disappointments and failure as we have done little more than pursue the status quo. I sincerely hope that we collectively make better, and braver, choices in the next decade.
– Bill H.