Lyme on the brink – the battle for a vaccine

 

After getting quite a lot of reads of my tick-borne Powassan virus post of two weeks ago, I decided to take a good long look at Lyme, which is not as horrific as Powassan but is thousands of times more prevalent. I wanted to know more about the bacterium that causes the disease, where it comes from, and what’s being done about it – moreso than the disease itself or its treatment.

The creature that causes Lyme is called Borrelia burgdorferi, named after researcher Willy Burgdorf, who first found it in 1982. It’s a long and skinny spirochete bacterium – meaning it’s spiral-shaped, allowing it to corkscrew its way from one place to another and efficiently drill into human tissue. It’s highly mobile and reproduces rapidly. Interestingly, it was the third microbe (bacterium, virus, fungus) ever to have its genome fully sequenced, so we know quite a lot about it.

1024px-Borrelia_burgdorferi_(CDC-PHIL_-6631)_loresThe Lyme disease-causing spirochete Borrelia burgdorferi – about 1/50 millimeter long by 2 or 3 micrometers wide (CDC photo)

Here in the Northeast, it thrives happily in the blood and tissue of the white-footed mouse, which doesn’t in the least bit mind serving as its reservoir. This mouse, rather than deer or other animals, is the principal source of the pathogen. And deerticks (the blacklegged tick, Ixodes scapularis) love to feed on white-footed mice, thereby ingesting the bacteria into their gut.

I’ve also done just enough research on ticks to learn there’s no one out there who feels we need them. We just don’t. Guinea hens cheerfully eat them (and sources say a single guinea hen will clear one whole acre), but almost nobody else will take the chance. Ticks diminish certain animal populations, like moose (and they are brutal on moose!), but no one is saying we have too many moose in northern New England. Ticks seem monstrously unnecessary in nature, they’re disgusting, and not just a little bit scary in what they can do to us. And every year there seems to be more of them around us.

The LYMErix Debacle: 1998-2002

It’s appalling and ironic that we can vaccinate our pets against Lyme, but not ourselves. That wasn’t always the case. Until twelve years ago, we had access to a Lyme vaccine made by SmithKline Beecham, and about 1.4 million people used it. Launched in 1998 under the name LYMErix, it had the blessings of the FDA and the CDC’s Advisory Committee on Immunization Practices (ACIP). It was ingeniously designed and worked quite well. But the ACIP also noted some issues with the drug, like -

  • vaccine efficacy was noted to be only ∼80% against definite disease outcome
  • 3 doses were required over the first year, meaning there wasn’t full protection until the second year
  • safety data were lacking for people under 15 – a high risk group
  • the vaccine was only for Borrelia burgdorferi – the North American strain

(For an excellent, highly detailed account, see Vaccines against Lyme Disease: What Happened and What Lessons Can We Learn?” by Gregory A. Poland, in Clinical Infectious Diseases, Oxford Journals)

The FDA had similar concerns, but its panel gave the drug a unanimous thumbs up.

LYMErix

You’d think the public would be thrilled to have this drug, but that’s not how it played out: reports started to circulate that LYMErix caused arthritis and other side effects, and soon enough anti-vaccine activists and lawyers got involved to file a class action suit against the drugmaker (now GlaxoSmithKline). Despite the FDA’s and CDC’s assertions that the complaints were baseless, damaging publicity spread, public demand for the vaccine plummeted, and in February 2002, seeing it as no longer economically viable, Glaxo pulled LYMErix off the shelves – a victim of the people it was trying to help. (I should note that the battle over LYMErix was exceptionally contentious and controversial – I’ve offered only a thumbnail sketch of what happened. Another vaccine developer, Pasteur Mérieux Connaught, was about to launch its own Lyme vaccine, but was so discouraged by the LYMErix debacle it didn’t pursue licensing).

2013: Enter Baxter Healthcare

With Lyme infections climbing through the 2000s to an estimated 300,000 a year in the U.S., the Vienna-based biotech company, Baxter Innovations, (a unit of Baxter Healthcare of Deerfield, Illinois), in collaboration with Stony Brook University and Brookhaven National Laboratories, developed a new and more broadly effective vaccine candidate that it characterizes as “a novel multivalent chimeric antigen” (an antigen is an antibody generator). The drug was tested on mice in 2011, then in Phase I human clinical trials with 300 adults in 2013 – three main immunizations and one booster each, of different dose levels. The results? “Predominantly mild adverse reactions and no vaccine-related serious adverse events.” Interestingly, Baxter tested the drug half with aluminum hydroxide adjuvants, half without (an adjuvant is an additive designed to stimulate a person’s immune response, thereby boosting the efficacy of the antigen).

Let’s dig into this antigen little further. First, it’s called a recombinant OspA: it’s a gene made from the outer surface protein A of the cell surface of the Borrelia burgdorferi spirochete itself (the North American strain), and then bioengineered (variously cloned, ligated, spliced) with outer surface proteins from the two main European strains, so that it becomes a little bit of each, conferring immunity against Lyme both here and in Europe.

F1.largeBaxter’s new Lyme-fighting protein, far right: a “chimeric” gene-spliced blend of the outer surface proteins of both the North American (OspA-1) and European Lyme bacteria (OspA-2) (Image: Stony Brook University School of Medicine)

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To drill down just a little deeper, here’s the “multivalent chimeric” part of it: it’s multivalent because it will protect an individual from more than one strain of the bacterium. It’s chimeric (which comes from chimera, an organism with two different blood types or genomes – very rare in nature) because it’s a recombined structure of outer surface proteins from different Borrelia strains. In the end, it’s a brand new organism – an antigen that mimics the Borrelia spirochetes convincingly enough to activate human antibodies against the real thing, when a tick expels it into you while feeding.

For my research for this piece, I sought the help of Baxter Healthcare itself, but they did not respond to emails and a phone call to their media contact. No surprise.  Baxter is a publicly traded company, this vaccine is a big deal for them and their partners, and they’re bound by laws and ethics not to reveal much of anything. Mainly, I wanted a ballpark forecast of when the drug might be available – assuming trials and approval processes went smoothly. Not a chance of getting that information from Baxter, but experience shows it may be another two or three years, at best.

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There’s still a lot we don’t know. We don’t know if the vaccine will sail through Phase II trials, get FDA approval, or have the full support of the CDC. We don’t know when it’ll be available, or what it will cost. We don’t know if the final version will require more than one vaccination (clearly LYMErix suffered from its protocol of three doses in one year). And, although its first clinical trials were very successful, we don’t know what side effects may show up in a much larger, general population. We also don’t know how organized and angry the opposition may be (see here for a fine article from Truthout.org on the “Lyme community”‘s views of the FDA and the CDC).

Still, for Baxter and Stonybrook and Brookhaven, all the lights are flashing green. And as soon as they’re willing to talk, we’ll know a lot more.

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(Tip o’ the hat to my wife Carla, an MPH and public health worker for many years, for her help researching this piece.)

 

 

 

 

 

 

 

 

Ned White

About Ned White

Ned White is an author, photographer, crossword constructor, humorist, traveler through 49 states, and an avid cook. He lives with his wife in South Thomaston.