A new report from the Scripps Institute in La Jolla, CA, describes a vaccine they have made against heroin. To make such a small molecule immunogenic, they coupled it to a foreign protein (making the heroin therefore into one more antigenic determinant on a large antigen) and added some adjuvant to boost responses. In animals, the vaccine was very effective in blocking the action of heroin. A neat twist: heroin is metabolized rapidly in the body to several related and active products, and the vaccine also degrades in the tissues, so that animals responded by making not only antibody to the initial, heroin, vaccine, but successively to the degradation products that remained attached to the protein and so were still immunogenic. They call this a "dynamic vaccine."
The next step would be to develop a version that could be used in people. Maybe it could be used after someone has completed a course of conventional detoxification therapy, to prevent a relapse (one assumes that they would simply not get a high from the drug, which would be neutralized by antibodies). On line, someone has already suggested giving the vaccine to every child at birth! I don't think that's going to happen. And I do worry about what someone with a strong addictive tendency might come up with to defeat the immunization...
Wow! The timing is ironic since Amy Winehouse was just found dead (and known to have many addictions)...I do have a couple of questions...
ReplyDeleteHow well would this work following a infusion of heroin? It takes time to make antibodies...would it be a case of too little too late? We know antibody half-life is about 3 weeks...so it wouldn't be due to pre-formed antibodies.
Do we know whether, as you suggested above, the antibodies would neutrolize the heroin rather than work via competitive binding, thus developing a new heroin-like substance?
Thanks for this interesting post!!
Poor Amy, what a waste...
ReplyDeleteYour first question is a really good one: but somehow we go on making antibody long after antigen is easily detectable; for example, 10 years after a tetanus booster! Clearly there are plasma cells pouring out antibody for a long time, even though IgG has a half-life of 3 weeks.
And I guess you can't be sure that the antibody would actually neutralize the heroin until you tested it. But I'd think that heroin, being about the size of a typical antigenic determinant, would be covered up pretty well by a specific antibody.
Zoe: In the paper, it showed antibody titers dropped by half after about 50 days (after following a 4 dose vaccination plan over 53 days).
ReplyDeleteIt seems like this would need very frequent boosters, maybe every other week, in order to maintain antibody titers.
One potential problem I could see is the fact that they also incorporate a morphine-like hapten; meaning that people would develop antibodies to morphine, a very commonly used analgesic, especially in emergency conditions. A person on this vaccine could be in trouble if they were in some sort of accident and needed morphine legitimately. In addition, if the person were unconscious, how could they tell medical personnel that they were on the vaccine?
The group said that the antibodies were not cross reactive for oxycodone or codeine, related opioids, which could alternatively be used if legitimate medical need arose. However, oxycodone, hydromorphone, fentanyl and oxymorphone are all other strong opioids that are illicitly bought and sold. What would stop a person on this vaccine from simply using a drug that the vaccine didn't cover (such as the above mentioned)?
S. Brookshire PSIO 495K
MedicAlert-type bracelets could be useful.
ReplyDeleteYou bring up good points, SB. Do you think this idea has any possibility of getting into human treatment or prevention? Is it similar ethically to the use of Antabus (disulfiram), a drug that recovering alcoholics voluntarily take, which makes them violently ill if they take a drink?
Sounds like a useful treatment for recovering addicts who are willing and have a functioning and able immune system. I imagine other health issues being prevalent in these individuals. If the immune system is compromised, making an addict unable to mount a proper adaptive response, then the vaccine may fail to be effective. Also, the addictive behavior of rats may be different from humans. Isn't it possible that a patient may self-administer at an ever increasing level, in an effort to "out do" the vaccine, and end up overdosing?
ReplyDeleteI really like the use of a "dynamic vaccine" and how the antigen degrades in the body in the same fashion as the target molecule. What other vaccines work in this style and how could this idea be used in other vaccines? How about an antigen, made in the lab, that parallels the development of say a virus coat or the metabolic by-products of certain pathogenic bacterium. The vaccine could be made to develop inside the patient and be effective at any point of infection. Imagine!
I wonder how many nicotine vaccines have been buried by big tobacco?