OK- Let's Reexamine Assumptions About H5N1 Risk of Severe Infection, Immunity, and Protection (Maybe?) in Mammals Previously Infected with H1N1
Ferret work from Pittsburgh demonstrates protective effect of prior H1N1pdm09 infection on later cow/Tx/24 H5N1 virus inoculations
Michael Coston of Avian Flu Diary is my Number One source by far for cutting edge research releases as they hit preprint. The paper he posted yesterday hit the jackpot for raising a whole host of new questions as we try to make sense of what we’re seeing (or not seeing) in both people and animals as mammalian H5N1 2.3.4b B3.13 explodes across the world. Please read Michael’s blog, then the paper itself, before I raise some questions as I think about some of the contradictions and incomplete picture within our limited observations as we attempt to unravel this issue.
The preprint:
I won’t even attempt to make sense of “original antigenic sin” or neuramidase protection” or cellular versus humoral immunity in my thoughts, leaving that to Michael’s blog and his references. I’ll also leave discussions regarding relative human susceptibility to medical experts, although partial protection through prior influenza exposure is certainly a plausible and hopeful explanation for why we may see less transmission and clinical illness from the current H5N1 in humans likely pre-exposed to H1N1 seasonal flu earlier in life.
However, turning to animals, this research raises some interesting questions we can address. First, regarding pigs - are pigs relatively resistant because most have been exposed to H1N1 (or H1N2) early in their lives, thus providing some relative natural resistance to H5 infection, or at least resistance to shedding and onward transmission and detection of H5 variants? Even if one pig becomes infected, unless it spreads onward multiple times, the odds of detection are negligible because the pig population as a whole is resistant from H1 exposure. This would remain true unless the H5 genome should in some way mutate to become relatively more infectious in the swine respiratory system than multiple competitive H1 clades now occupying that space. A second threatening factor could be if the relative “protective” effects of previous H1 exposure in swine should be compromised by further changes to the H5 genome, allowing it to multiply.
The overriding point I take from the paper is that viral pathogenicity in any mammalian livestock species is only one factor in the degree of morbidity and mortality risk in individuals in the population. Under laboratory conditions utilizing known naive infectious status animals, H5N1 infection is likely to be fatal - e.g. lab mice, naive ferrets. The virus itself is lethal and increasingly able to cross into mammalian species; however, in the real world, species that have had exposure to H1N? mammalian viruses, whether recognized as clinically ill or not, MAY have some partial or nearly total protection from H5 mortality, decreased morbidity, and perhaps less shedding of infectious virus into the environment.
This type of phenomena could help explain why:
Not all cats exposed to H5 on dairy farms die, or even show illness
Mice in the wild seem to survive in some cases, perhaps spreading virus onward for a period of time, while lab mice, raised in controlled environments die
Not all cows and replacement stock on dairy farms seroconvert to H5 after herd infection, perhaps due to partial (non-serological) protection from sporadic human H1 exposure
This same partial cellular-based protection could extend to protecting a majority of lactating cows from secondary mastitis following primary H5 infection by still unclear means (oral, respiratory, conjunctival?). Note that in the Pittsburgh study, the pre-infected H1 ferrets’ lesions from H5 infection were confined to the respiratory tract.
I used this simple diagram when I started this blog for a reason. Disease is in interaction between 3 factors- host, pathogen, and environment. Within the host, there is the complex issue of susceptibility, which is mediated by both the pathogen and the environment. Importantly, hosts have long memories! We call it immunity, and we often forget it, don’t fully understand it, or ignore it when making observations. We may need to reset our thinking about the H5 threat in farm animals and mammals in general to account for the complexities of “partial” immunity from its influenza A relatives and the immunological roles they play in our complex ecosystems.
None of this speculation is proven or simple, but neither are our early assumptions! This research gives us all a fresh set of data with which to refresh our observations, then keep digging.
John