From: Mouwenda, Y.D., et al (2021), “Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon”, PLoS Neglected Tropical Diseases 15:10.
We all know how vaccines work. You take something from the pathogen into your body, triggering your body’s immune response to fight it off. Then, when you encounter the pathogen for real, your immune system, thanks to your Memory T-Cells (and a few other cells), is ready for it, and can fight it off easily.
There are a few ways to go about this process. Traditionally, the bacteria or virus causing the disease would be killed (‘inactivated’ for viruses, because they’re not quite alive to begin with) or knocked down to a less dangerous form (‘attenuated’). Once that was done, the pathogen could be injected (or swallowed, in the case of the Sabin Polio vaccine) into the body, triggering the required immune response without any danger to the patient. Indeed, many nineteenth century bacteriologists considered the ability to make a vaccine from a bacterial culture an essential skill that every bacteriologist should learn!
More recently, we’ve developed a very exciting technology called mRNA vaccines, which trigger your own cells to produce the virus’s ‘spike protein’, which then triggers your immune response against the spike. This is especially cool, because the spike is what the virus uses to infect your cells, so having your immune system able to recognise and disable it is a perfect way to protect yourself! The spike protein is harmless without the rest of the virus to go with it, as well, so there’s never any risk to you. The COVID-19 vaccinations I hope you’ve all had (if you’re able) are mRNA vaccines.
But what do you do when you’re trying to vaccinate against something that has no spike protein, and can’t be safely put into the body? Parasitic worms are a huge health problem in many parts of the globe, and are experts at evading the human immune system. It’s not entirely clear how they manage it, but many worms will not provoke an immune response, and giving everyone in an at-risk area drugs against them at once has become the main method used to protect people, despite the many obvious difficulties of such an endeavour.
One particularly nasty set of parasitic worms are the hookworms (Ancylostoma and Necator spp.). These live in the upper gut, where they feed off their unfortunate host’s blood, causing a whole host of problems, principally including anaemia. As I mentioned, they’re very good at evading the immune system, so to create a vaccine against them, scientists have had to get clever.
One promising approach is to train the immune system to recognise the enzymes (chemical tools) the hookworm needs to live. Trials have shown promising results for two enzymes, Na-GST-1 and Na-APR-1, which the hookworm needs to digest blood. As humans don’t drink blood we don’t have these enzymes, so their presence is a sure indicator of hookworm. And they are essential for the hookworm to feed, so training the immune system to knock them out will kill the worm in no short order.
Trials of these two enzymes have shown them to be safe and to provoke an immune response, indicating that they could be used in anti-hookworm vaccinations. Yoanne Mouwenda’s team wanted to dig deeper, and see exactly how the immune system responded to them.
Studying 24 people in Gabon, they found that unvaccinated people (at baseline) did not show any T-Cell response to Na-GST-1 (other immune cells did respond), but did respond to Na-APR-1. After three doses of vaccine, the participants T-Cells responded much more strongly to Na-GST-1, but had not changed their response to Na-APR-1. This suggests that Na-GST-1 is the better vaccine candidate, but it is difficult to be sure on such a small study, and it may be that Na-APR-1 might be just as effective when given in higher doses or a different form. The authors suggest that as the participants lived in Gabon, where hookworm does occur, they may have already developed a slight immune response to Na-APR-1 from natural infection.
Immunology is incredibly complicated, and I don’t understand half of it, but it is heartening to see scientific ingenuity on this level being brought to bear on protecting people from such a horrific disease.
And please, get every vaccine you are eligible for. Of all our medical technologies, they are by far the most effective and least risky, and save lives – maybe including yours! – every day. And most of the people saved by vaccination don’t even realise they were ever in danger. Which is nothing short of miraculous, thinking about it.