In the 1960s, an attempt to make a chlamydia vaccine backfired spectacularly, increasing vulnerablity to the disease. For the first time since then, researchers think they know what went wrong, and the explanation has led them to a promising candidate for a successful vaccine.
Chlamydia, unlike most diseases we vaccinate against, is a genus of bacteria. It infects many animal species, and Chlamydia trachomatis, a sexually transmitted human pathogen is the most common cause of preventable blindness in the world.
Chlamydia infections respond to antibiotics if caught sufficiently early, but many symptoms, such as infertility, are seldom detected in time. Most people recover from a chlamydia infection without symptoms, but in the meantime can infect sexual partners. In the US alone a million infections were reported in 2013, making it, in the Centers for Disease Control and Preventions' words, “the most commonly reported notifiable disease in the United States.”
Moreover, broad spectrum vaccines against chlamydia could save many endangered species, most famously koalas.
Around the time the first measles and mumps vaccines appeared, trials against chlamydia provided short term protection, and reduced scarring. However, some people actually became more susceptible to chlamydia after being vaccinated. Nervous and confused, scientists dropped further trials.
In Science, a team led by Harvard Professor Ulrich von Andrian announced a vaccine against chlamydia in mice. “This is really a very surprising and exciting observation,” said von Andrian. “We used this vaccine to try to really understand an immune response that was previously not that well worked out. Now our vaccine gives very good protection, even against different chlamydia strains.”
Like the Salk polio vaccine, the '60s chlamydia vaccine used killed versions of the infectious agent. No longer able to breed, the injected bacteria couldn't create an infection, but the body's immune system could learn to recognize the invaders, generating cells ready to deal with a live dose.
The problem with previous vaccines, von Andrian's team argue, is that chlamydia infects mucosal surfaces, such as the eyes and inside of the mouth. When the dead bacteria are first encountered within muscle or skin, the immune system remembers this context along with the bacteria, and becomes confused when meeting the live version on a mucosal surface. Sometimes the out-of-context exposure even induces tolerance, so the immune system leaves the bacteria alone.
Consequently, it is essential to administer the vaccine via mucosal pathways – most realistically nasally or under the tongue. However, this has not been a guaranteed path to success in the past.
Von Andrian's vaccine is injected in conjunction with charge-switching synthetic adjuvant nanoparticles (cSAPs) which strengthen the immune system's response. While the use of adjuvants is standard for vaccines, cSAPs have the capacity to stick with the vaccine on the journey from a mucosal surface to the lymph nodes where the immune system is trained to recognise invaders.
“Mice that were given the cSAP vaccine very quickly eliminated chlamydia and were even faster at completely clearing it than the animals that had developed natural immunity after a previous infection,” von Andrian said.
The technique unleashes two waves of immune response, one of which resides in the uterus of female mice, ready to tackle the sexually-transmitted infection should it reach the mucosal walls of the vagina. For a sexually-transmitted disease, this is excellent positioning. The second type of immune cell circulates in the blood and can tackle infections anywhere.
Von Andrian acknowledges that, given the history, “It will be very hard to convince anyone to try your vaccine unless you can explain why there might have been this paradoxical effect 50 years ago and why we are confident that this paradoxical effect will not be observed with the current formulation.” However, he believes that his team have the answers, having achieved success in mice with humanized immune systems, as well as conventional mice, and have licensed the technology to biotech startup Selecta Biosciences.
[H/T The Verge]