Vaccines have been a ‘hot’ topic around the globe in light of the Covid-19 pandemic, and in the apiculture world research towards American foulbrood (AFB) ‘vaccines’ has piqued beekeeper interest. Science writer Dave Black looks at the cutting-edge science involved in developing honey bee vaccines.
Covid19 has been credited with ushering a ‘new age’ of vaccines by companies including Moderna recently. The mRNA (messenger ribonucleic acid) vaccines that were developed at impressive speed might be a tribute to the focus a pandemic and government’s blank cheques can achieve, but it has also enlarged the concept of ‘vaccines’, as commonly understood, to the point where they are no longer just about preventing infectious diseases.
Moderna are promoting the idea that by the end of the decade (!) ‘vaccines’ will be in use treating cancers, cardiovascular disease, and autoimmune disease, and who knows what else[i]. These treatments will effectively retrain our immune system to detect and respond to entirely novel threats it knows nothing about. Given the number of trials, the amount of money involved, and results that inspired the US FDA to take notice, the hype isn’t completely unjustified.
For Beekeepers, the promise of an ‘AFB vaccine’ has surfaced, with Dalan’s product enjoying ‘conditional’ release in the US, but hardly universal approval in the apiaries. Some of the limitations from a New Zealand perspective were discussed in this magazine in February, and there are also issues that arise in a global trading environment where money and not health complicates the regulatory setting. While the AFB vaccine benefits from the general excitement around vaccines at the moment, the examples of Avian bird-flu and Foot & Mouth disease illustrate the complexity of the international commercial circumstances when it comes to introducing animal and not human vaccines.
Back in January I had a look at insect immune systems and made the most cursory mention of ‘immune priming’ which is the sort of idea that lies at the heart of new invertebrate treatments. As we don’t really know how it works it’s described as ‘priming’ the immune response in a very general sense, and while insects don’t produce antibodies that can be transferred to their offspring there is also evidence of a kind of ‘memory’ of infection being passed from one generation to the next.
How’d Ya Know That?
Trans-Generational Immune Priming (or TGIP) is simply the transfer of a parent’s immunological ‘experience’ to its progeny. So, for honey bees, some knowledge about the pathogens in the environment the queen and or drone had to survive is being passed to their offspring. So far, in ‘bees, TGIP has been studied with bacteria (including both American and European foulbroods), and viruses (deformed wing virus). It isn’t clear if some immunologically active compound (like an antibody, but not) can be transferred, or whether it’s merely a ‘signal’ that elicits a response, or whether it’s both. One implication is that TGIP is going on all the time naturally, unassisted and, until now, un-noticed.
The first evidence for the idea was only published in 1999 and most studies (there aren’t many) date from the last ten years or so. They are all very different, and not just different invertebrates and different pathogens. Comparisons are difficult to make. There are some things to think about when you hear the topic come up. We have to wonder if the infection route was relevant or just convenient, about the infectious material used, how much and does it matter if it was dead or alive? Which parent was doing the ‘priming’? and how the effect, if any, was demonstrated?
In the first honey bee/AFB study[ii] the researchers decided to use an ERIC-II strain of the bacteria (because it kills larvae faster), although it is arguable that the ERIC-I strain might be more important, as it’s more widespread (New Zealand has both). Physiologically the strains might be similar, epidemiologically they are not. The queens had been injected with a solution containing vegetative bacteria (not spores) that had been killed by heating them, and that (the injection) might raise an eyebrow too. The results suggested a 26% improvement in the survival of ‘primed’ larva when exposed to a diet containing 20 spores and suggested that was correlated with an increase in the production of a particular type of immune cell. A similar study, using EFB bacteria more recently, was unable to find any effect on larval survival at all, so we are left wondering why the studies differ.
The Great Unknowns
But beyond individual studies, besides the mechanism being unknown, we also don’t understand what effect it has on the epidemiology of any disease, or how TGIP evolved and will continue to evolve. The parental ‘ability’ must be one expressed by genes, so we’d expect that it would vary among individuals, and be subject to natural selection. Some individuals may be better at ‘priming’ than others. If the priming has a variable effect what does that mean for the virulence of the pathogen. How does the pathogen evolve given the arms race between pathogen and ‘primed’ host?
There are questions about costs and benefits. In what circumstances is it good that the offspring are ‘educated’ about threats from the parent’s environment, when that ‘education’ must come at a cost incurred whether or not the pathogen turns up? A study involving Bombus terrestris (buff-tailed bumble bee) appears to show immune priming was effective for a bacterial infection, but it reduced immunity to another parasite, Crithida bombi. What circumstances drive TGIP selection if it is costly?
While immune priming, and Trans-Generational Immune Priming, promises to be a thought-provoking and lucrative field of study about a previously unsuspected aspect of biology, it might be worth asking if applying the emergent science in our apiaries is any more than a premature proof-of-concept. If an AFB vaccine is possible, why is that a ‘good thing’?
Dave Black is a commercial-beekeeper-turned-hobbyist, now working in the kiwifruit industry. He is a regular science writer providing commentary on “what the books don't tell you”, via his Substack Beyond Bee Books, to which you can subscribe here. i Guardian 7th April 2023, Cancer and heart disease vaccines ‘ready by end of the decade’. https://www.theguardian.com/society/2023/apr/07/cancer-and-heart-disease-vaccines-ready-by-end-of-the-decade ii Hernandez Lopez J, Schuehly W, Crailsheim K, Riessberger-Galle U. 2014 Trans-generational immune priming in honeybees. Proc. R. Soc. B 281: 20140454. http://dx.doi.org/10.1098/rspb.2014.0454