Hendra: why not just go ahead and vaccinate? Benefits - the vaccine

Hendra: why not just go ahead and vaccinate?

Benefits

Experimental vaccine challenge study

An experimental vaccine challenge study was published in 2014, in which 10 horses were exposed to 2 million units of HeV (isolated from the 2008 Redlands outbreak) via the nose and mouth, either 3 weeks or 7 months after vaccination*. Four additional horses were not vaccinated and served as the 'control' group; they were exposed to the same amount of virus.

* Vaccination consisted of 2 vaccines, given 3 weeks apart. (Note that the current primary immunisation series includes a third vaccine, to be given 6 months after the second.) Seven horses received the full dose (100 micrograms), whereas 3 horses were given a half dose (50 micrograms).

All 10 vaccinated horses remained healthy for the 7 to 9 days after viral challenge (the length of the observation period in this study), whereas all 4 unvaccinated horses became ill between days 5 and 7 after viral challenge.

However, it's important to note that all of the horses in this study were euthanised ('put down') between days 6 and 9 post-challenge, so we have no way of knowing what would have happened beyond that point.

None of the vaccinated horses challenged 3 weeks after the second vaccine had any viral material in their body fluids (oral, nasal, or rectal swabs, urine, manure, or blood). One of the 3 horses challenged 7 months after vaccination had a small amount of viral genetic material (HeV genome on PCR*) detectable in her nasal swabs between 2 and 7 days after challenge. However, the authors didn't consider the amount of material significant, and the mare was negative on PCR for all other body fluids and tissues (collected postmortem).

"We conclude that the level and pattern of virus replication in the 1 vaccinated horse do not meet the epidemiological criteria presently associated with transmission of infection to humans."

* PCR = polymerase chain reaction, a test used to detect the presence of genetic material (in this study, viral RNA); note that PCR does not distinguish between live/infective and dead virus.

In short, not only did HeV vaccination protect against illness, it prevented meaningful shedding of virus in the horses' body fluids.

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But the devil, as they say, is in the details... This study seems to suggest that the amount of G protein in the commercial vaccine (100 micrograms per dose) may be higher than it needs to be. It also raises the question of whether high antibody titres really are needed for protection against HeV in real-world situations.

None of the vaccinated horses became ill nor shed significant amounts of virus, but individual responses to vaccination were highly variable among horses.

Blood samples were taken immediately before viral challenge and HeV-specific antibody titres were measured in duplicate for each horse.

In the 7 horses challenged 3 weeks after the second vaccine, individual titres ranged from 128 to over 4,096 (the upper limit of the assay). That's more than a 10-fold difference among the horses. (Titres are serial dilutions, where each successive dilution is 2 x that of the one before, so the maths are a bit odd. There are 5 'doublings' betweeen 128 and 4,096.)

In the absence of any further viral challenge, antibody titres decline fairly predictably over time, so the higher the starting point, the longer protective levels of antibody persist in the bloodstream. This is a key aspect of duration of immunity which determines the recommended booster interval for a particular vaccine. (More on that with the next study.)

In the 3 horses challenged 7 months after the second vaccine, the titres were much more consistent; in all 3 horses the prechallenge titre was 16–32.

These 3 horses "were selected from 29 vaccinated horses in a larger field efficacy and safety study on the basis of temperament and for having the lowest serum neutralization titers in the group at the time." The field study the authors referred to isn't mentioned in the paper, but it is probably the one describe on the next page, as no other field studies of HeV vaccine efficacy and safety in horses have been published thus far.

It's to be expected that titres would be lower several months after vaccination than those measured just weeks after vaccination. However, this small study showed that a titre of 16–32 was protective against illness in the face of massive challenge with HeV, at least in these 3 horses. This low a titre also prevented viral shedding in 2 of the 3 horses challenged 7 months after vaccination, and limited viral shedding to an insignificant amount in the third horse.

It would be good to know how the horses' antibody titres changed in the week or so after viral challenge. Unfortunately, no such data were collected in this study.

In the 2018 study of diagnostic methods I mentioned in relation to the development of naturally acquired immunity, 9 of the 11 horses with two or more blood samples showed an increase in HeV antibody titre between paired samples taken about 1 week apart. One horse showed a decrease (from > 32 to 16) and the other horse had persistently high titres (2,048 in 4 samples taken over 2 weeks). We don't know where any of these horses were in the timeline between viral exposure, infection, and recovery, but in 10 of these horses it's a fairly safe bet that they were mounting an active immune response to current viral challenge.

Duration of immunity is about more than maintenance of high antibody titres; it's also about cell-mediated immunity, which is broader and both more immediate and enduring than antibody production, yet it was not evaluated in this challenge study.

Here is what the researchers who conducted the field study had to say about this experimental vaccine challenge study:

"Under laboratory conditions, the horses with serum-neutralising antibody titres (SNT) as low as 16 were protected from infection. It is possible that protection from field exposure to virus may also occur in immunised horses with lower (or even undetectable) titres. The reasons for this include the rapid time-frame over which extensive mucosal [oral and nasal] exposure to infective fluid occurs under experimental conditions and the fact that protection will depend upon the development of an anamnestic [cell memory] response, in addition to pre-existing antibody levels."

The second thing worth noting is that even the half dose of the vaccine (50 micrograms instead of 100 micrograms) protected against illness and prevented viral shedding in body fluids following viral challenge 3 weeks after vaccination.

Of the 4 horses who received the full dose of vaccine and were challenged 3 weeks after vaccination, 2 horses had titres of 512–1,024 and the other 2 horses had titres of more than 4,096.

Of the 3 horses who received the half dose, 1 horse had titres of over 4,096; another had titres of 2,048–4,096; and the third horse had titres of 128–256. None of these horses became ill or had detectable virus in any of their body fluids or tissues after challenge.

This experimental study used a huge dose of HeV to 'challenge' the vaccine. It is encouraging to know that even half the recommended dose protected the horses from illness and prevented them from shedding meaningful amounts of HeV in their body fluids. However, we need to know more, particularly about duration of immunity and whether annual boosters really are necessary.

Immunological studies in dogs and cats have resulted in sweeping changes to the recommended vaccination schedules, particularly in regard to booster intervals. For example, in adult dogs it is now recommended that boosters for the core vaccines (distemper, hepatitis, parvo, parainfluenza) be spaced at least 3 years apart, rather than the customary annual boosters.

The guidelines also state that "[m]easuring antibody levels (quantitative or qualitative) provides a reasonable assessment of protective immunity against CDV [canine distemper virus], CPV [canine parvovirus], and CAV2 [canine adenovirus type 2, which cross-protects against canine infectious hepatitis virus]." Similar recommendations are made for adult cats.

It's unwise to extrapolate from one species to another, such as from dogs to horses, without good studies that show relevant similarities. But comparable research in horses hasn't even been done yet.

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