lundi 12 octobre 2015

Research Raises Prospect Of Springtime Shot To Protect Against Lyme Disease

Research Raises Prospect Of Springtime Shot To Protect Against Lyme Disease

lymedisease

“Sign me up!”

That was my first, emphatic reaction to word that University of Massachusetts Medical School researchers are making progress toward a shot that we here in Lyme disease territory could get every spring for months-long protection through high tick season. It would use monoclonal antibodies — medical cruise missiles that can hit the narrowest of targets.

Sadly, the research, though promising, is still only in mice, and it will be years before such a shot could possibly be available in humans. But for those of us eagerly awaiting better protection against Lyme disease — not to mention those of us frustrated by this: Why your dog can get vaccinated against Lyme disease and you can’t — it’s heartening news nonetheless.

I asked for details from UMass Medical School professor Mark Klempner, a longtime Lyme disease researcher and executive vice chancellor of MassBiologics, a non-profit, UMass-affiliated maker of vaccines and other public-health-oriented medicines. His colleague, Dr. Yang Wang, just presented their team’s findings to a major conference on infectious disease in San Diego. His summary:

“For the past two-and-a-half years, MassBiologics has been developing a new approach to prevention of Lyme disease, as part of our overall public health efforts to protect the citizens of Massachusetts and beyond for diseases of interest.

We’ve taken a different approach than the vaccine approach, and what we’ve developed is a human monoclonal antibody that, when present in the blood of a host, will prevent the transmission of the Lyme disease bacteria from the tick to that host.

I want to emphasize that so far these studies have been done exclusively in animals — so-called preclinical studies — and our future is to move this into clinical studies, which we will hopefully initiate in 2016.

The idea here is based on a couple of precedents. The first is: We know that the previously available [Lyme disease] vaccine worked by inducing many, many different antibodies, only one of which was important in the protection. And similarly, we know that there is a precedent for being able to give a safe and effective monoclonal antibody to young babies in order to prevent them from getting a different infectious disease called Respiratory Syncitial Virus.

So for both precedent and safety reasons, we chose to go after a single monoclonal antibody that would be able to prevent the transmission of Lyme disease during the entire season. The monoclonal antibody idea has additional benefit in that when the vaccine was available, it required three shots over six months to induce immunity, and so you needed to start to take the medicine sometime in the winter in order to be able to protected in the following fall, and there was not a lot of uptake of that.

Dr. Mark Klempner (Courtesy UMMS)

Dr. Mark Klempner (Courtesy UMMS)

So here, one of the advantages is that the antibody, if we give it to you, provides you immediate immunity, as it does in a mouse, and it should last for the entire season by engineering the antibody to have a very, very long half life. And then it would be gone at the end of the season, and the next season you would take the medicine again and it should work again for the entire season.

The overall mechanism of the way the antibody works is quite interesting and unique, and it’s really based on the idea that the way you catch Lyme disease is, obviously, by the bite of the tick, and what happens in the tick when it drinks your blood is that there’a a sudden explosion of the organisms in the intestine of the tick, where they begin to multiply very quickly; they change somewhat and then they invade the tick gut and move to the salivary gland, where, during the feeding process they can then be deposited in your skin, where you get that typical bullseye rash, often.

So here the idea is that if you have the circulating antibody going around when the tick bites you, it then drinks in a little bit of your blood and contained within that blood is the medicine that kills the bacteria right in the gut of the tick and thereby prevents transmission.

When we do these studies in mice, that’s exactly what happens. There is absolutely no transmission from ticks onto these mice. We put six infected ticks on the mouse and see if they can transmit Lyme disease to the mouse, and when we pre-treat the animal with the antibody, there is no transmission. When we use an irrelevant antibody that has nothing to do with Lyme disease, there’s no protection, and therefore we know that this is quite specific for prevention of Lyme disease.

We call this pre-exposure prophylaxis to distinguish it from a vaccine, because we’re giving the very specific preventative antibody to the animal — and hopefully to people in some years to come; so before you would be exposed, you would be prevented from acquiring Lyme disease.

I do want to emphasize that we’re at the pre-clinical stage so we don’t want to over-hype this in any way, and we’re hopeful to move on to the clinical phase of development beginning next year.”

So, I asked, could I really sign up? They’ll be recruiting humans for a clinical trial next year?

Drug development generally involves a small initial “Phase 1″ study of safety, how long a medicine stays in the bloodstream, Dr. Klempner replied. That could indeed come next year. But it will clearly be several years before I can really sign up. He offered some encouragement, though:

“This mechanism is really quite unique and I think it’s important that a singular monoclonal antibody has been given for over a decade to highly vulnerable premature infants to prevent them from getting Respiratory Syncitial Virus. So the safety of administering monoclonal antibodies to an incredibly vulnerable population has been well established. Of course, any time you’re developing a medicine your first concern is safety — first, do no harm — and then efficacy. And that’s been the focus of all of our work, to make sure we were going down a path we could be quite assured would be safe and hopefully effective.”

He also noted that there’s no indication that the biological target in the bacteria is shared by humans, adding to hopes of avoiding side effects.

One point of terminology: This is not a vaccine, Dr. Klempner emphasized, it’s “pre-exposure prophylaxis,” or “PrEP”, a strategy that’s drawn particular attention lately with efforts to stem HIV by providing preventive drugs to targeted populations. It has been used with rabies and hepatitis prevention as well, he said: the basic idea is that you’re immune by virtue of having the antibody circulating in you before you’re exposed.

So how is that different from a vaccine?

“What a vaccine does is: you take the thing you’re going to be exposed to, and then you give people little pieces of it in order for them to develop immunity to it,” he said. “And what happens is that the immune system develops this wide array of preventative molecules, mostly antibodies, but it develops at least dozens, sometimes hundreds, of antibodies against the infectious material. But it turns out only one, maybe two, of those antibodies are relevant — the rest kind of come along for the ride; sometimes they induce side effects, like fevers. So vaccines induce the antibodies but they don’t induce only a specific antibody; they induce many, many antibodies.

Here, what we’ve done is said OK, let’s take away that upfront presentation of antigen first, but we’re going to go right for the specific antibody that is the one that prevents disease and just give that. And the big advantage, of course, is specificity and immediate immunity. Whereas with the vaccine your immune system needs to rev up and develop immunity — and in the case of Lyme disease that took at least six months — here, within minutes after you took that shot you’d be protected for the duration.

And how is it, I asked, that this discovery came now?

The key, Dr. Klempner said, was the idea to bypass the vaccine and go right to the antibody. “That really emerged from MassBiologics. MassBiologics, as you may or may not know, is a research and development unit of the UMass Medical School that has its origins as part of the Department of Public Health in Massachusetts. And for the past 15 years or so, it has focused on developing monoclonal antibodies for the treatment and prevention of disease. So it was that combination of being at a non-profit place that was founded on public health issues, and that has a long history of both discovering and developing monoclonal antibodies, that all came together to lead to this discovery.”

I guess this means I can’t complain quite so loudly about the relative lack of resources devoted to fighting Lyme disease given its magnitude as a public health problem. But still, for more on that, please see this excellent piece by Beth Daley of the New England Center for Investigative Reporting: Despite spread of Lyme disease, Mass. dedicates no money for prevention.

And just a bit more detail from the UMass Medical School:

To develop a human monoclonal antibody for pre-exposure prophylaxis of Lyme disease, Dr. Klempner, Yang Wang, MD, PhD, assistant professor of medicine, and colleagues created a panel of borreliacidal human monoclonal antibodies by immunizing mice that were transgenic for human immunoglobulin genes for a surface protein of B. burgdorferi.
They tested more than 90 monoclonal antibodies and picked four for further investigation, based on how well they killed the bacteria. Two of the four were selected for further study in vivo—both prevented infection of mice when challenged with infected ticks.
These studies suggest that OspA-specific human monoclonal antibody could provide pre-exposure prophylaxis for Lyme disease worldwide caused by a broad range of Borrelia genospecies, since the antibody target appears ‘highly conserved’—common across most species of Borrelia.

Readers, would you want the shot? Would you want the shot so badly you’d even sign up for a clinical trial?

Aucun commentaire:

Enregistrer un commentaire