Most medicine can be utilized for extra than simply the illness they have been initially designed to deal with. For instance, disulfiram (model title Antabuse) was developed to deal with parasites however has since been discovered to be helpful for treating alcoholism. It’s a lot faster and cheaper to “repurpose” medicine on this approach than it’s to develop them from scratch, which is why we now have dexamethasone – a steroid developed within the late 1950s – for treating extreme circumstances of COVID-19.

However what about vaccines? Absolutely they’re designed to solely shield towards a particular illness (or ailments, for mixed vaccines)? So why are researchers learning BCG (the vaccine towards tuberculosis) and MMR (measles, mumps and rubella) as a doable safety towards COVID-19?

Non-specific results

The understanding {that a} vaccine solely protects towards a particular an infection relies on what traditionally has been doable to measure: antibodies within the blood. These antibodies induced after vaccination have been proven to be very particular to the vaccine and so couldn’t shield towards different infections.

Immediately, we all know that the immune system is way more than simply antibodies. What challenged the concept vaccines solely have particular results towards a given pathogen was inhabitants research in west Africa.

In December 1979, a workforce of Danish scientists, led by our colleague Peter Aaby, adopted a bunch of individuals in Guinea-Bissau with common house visits. The principle focus was diet, however as a service to the inhabitants, the workforce additionally supplied the measles vaccine to all the kids.

The next yr, they observed that the measles vaccine decreased general deaths by greater than 70% – way more than might be defined by the prevention of measles, which precipitated about 10-15% of all little one deaths in Africa on the time. Different infections accounted for nearly all the opposite deaths. So the discovering might solely be defined if the measles vaccine additionally decreased the danger of dying from different infections.

These results have been named “non-specific results”. A seminal paper describing this discovery was revealed in 1984. The distinguished science journal Nature lists the discovering as milestone 13 in “Nature Milestones in Vaccines”.

Subsequently, our group in Guinea-Bissau began investigating different vaccines and a definite sample emerged. All dwell vaccines, that’s, vaccines that contained a weakened virus, such because the measles vaccine, have been related to a lot stronger reductions in mortality from any trigger than might be defined by the impact on the virus being vaccinated towards.

First, let’s have a look at the BCG vaccine. This vaccine is really useful at delivery in international locations that also have plenty of tuberculosis. However newborns with low delivery weight are normally vaccinated later. We randomly allotted newborns weighing lower than 2.5kg to obtain BCG at delivery or to obtain it later. Within the first month of life, we discovered that the danger of the newborns dying was decreased by greater than a 3rd in those that acquired the BCG vaccine at delivery.

Kids don’t die of tuberculosis within the first month of life, so the useful impact of BCG had nothing to do with safety towards tuberculosis. Fairly, BCG had decreased the danger of dying from sepsis and pneumonia – a totally non-specific impact. On account of our findings, the well being authorities in Guinea-Bissau modified their suggestion to stress BCG at delivery for all newborns.

The findings on the BCG and measles vaccines have now been reviewed by the World Well being Group. The WHO concluded that each BCG and measles vaccines cut back untimely loss of life general by greater than anticipated.

The oral polio vaccine is one other fascinating instance of non-specific results at work.

Giant scientific research of the oral polio vaccine within the 1960s and 1970s carried out in Russia confirmed that it’s efficient towards influenza, decreasing the danger of catching influenza by 60-80%.

Our group additionally examined the oral polio vaccine for its general well being results in Guinea-Bissau. In two randomised trials, we discovered that receiving the vaccine at delivery (versus not receiving it at delivery) was related to a 3rd discount in toddler deaths. We additionally discovered that the various oral polio vaccine campaigns within the final a long time have been a serious driver behind the unprecedented decline in little one deaths. As there was no polio an infection round in Guinea-Bissau anymore, it’s clear that these have been purely non-specific impact.

The innate immune system has reminiscence

The so-called “innate immune system” – the primary line of defence towards invaders – was not thought to have any “reminiscence” of earlier encounters with pathogens and so wasn’t thought to have any relevance to vaccines. (Vaccines depend on the “adaptive immune system” to work – the a part of the immune system that has “reminiscence”.) But latest analysis has proven that the innate immune system is strengthened when uncovered to sure vaccines.

As an illustration, in an experiment we carried out, we discovered that volunteers who had acquired BCG 4 weeks earlier than a yellow fever vaccine had a lot much less yellow fever virus of their blood than controls. This was as a result of the BCG vaccine educated the innate immune cells to turn out to be extra responsive and efficient.

These broad useful non-specific results of vaccines on the immune system might be helpful in a pandemic. Proper now many scientific trials are investigating whether or not previous vaccines, reminiscent of BCG, oral polio vaccine and MMR, can strengthen the immune system and cut back the danger of great COVID-19. A giant benefit is that we have now a few years of knowledge on these vaccines and we all know they’re protected. Additionally, they’re already made in lots of thousands and thousands of doses every year.

If it seems that a number of of those vaccines can present simply partial safety, it is going to be very welcome information for the world for present and future pandemics. It can even be a decisive blow to the assumption that vaccines solely shield towards the illness for which they have been initially designed.

The authors don’t work for, seek the advice of, personal shares in or obtain funding from any firm or group that may profit from this text, and have disclosed no related affiliations past their educational appointment.