FIP vaccines etc

This post is just some random musings about coronavirus vaccines, most clearly in cats. The rest is speculation.  As an introduction here is the abstract-like entry for a book chapter pulled up by Duckduck from 'tinternet. It sums up pretty much what I recall from back in the days when I was a clinician dealing with the horrible disease of Feline Infectious Peritonitis (FIP), derived from complications of Feline Enteric Coronavirus infection. No author is stated but if I was an editor looking to have a chapter written about FIP I would, without any doubt, send the request to Niels Pedersen, who authored this (very long and involved) review:

A review of feline infectious peritonitis virus infection: 1963–2008

The chapter abstract summarises the interesting bits of the Pedersen's review nicely:

Coronaviridae

In Fenner's Veterinary Virology (Fifth Edition), 2017

Immunity, Prevention, and Control

Feline infectious peritonitis is not controlled easily; control requires the elimination of the virus from the local environment, whether this is the household or the cattery. This requires a high level of hygiene, strict quarantine, and immunoprophylactic measures. Because kittens acquire the infection from their queens, early weaning programs have also been used in attempts to interrupt virus transmission.

The development of a safe and highly effective vaccine remains elusive, even with the availability of bioengineering approaches. The only commercially available feline infectious peritonitis vaccine contains a temperature-sensitive mutant virus, based on a serotype II virus. The vaccine is applied to the nasal mucosa to reduce virus replication and antibody formation. Under these conditions, a cellular immune response is favored, and some protection putatively is achieved. Vaccination of infected, seropositive adult cats is not effective. In addition, experimental challenge of vaccinated cats has resulted in “early death” due to feline infectious peritonitis in some cases.

A broad spectrum coronavirus protease inhibitor drug has recently shown considerable therapeutic efficacy for treatment of cats with feline infectious peritonitis, a finding that suggests the disease might in the future be treated with antiviral drugs.

What is clear from FIP vaccination is that antibody production (or the administration of hyperimmune serum or pure IgG antibodies) in the absence of a cell mediated immune response, is lethal on challenge of kittens with a field strain of FIP virus. The serum is harmless, the IgG is harmless, the vaccine is harmless. What matters is how the disease progresses when field virus meets the antibody replete host. The effect of a vaccinia virus vector vaccine was described here (you only really need to read the title, it says it all):

Early Death after Feline Infectious Peritonitis Virus Challenge due to Recombinant Vaccinia Virus Immunization

which could reasonably be described as a bit of a booboo.

To summarise: Vaccines which stimulate antibody production without stimulating cell mediated immunity are a problem. This is Antibody Derived Enhancement. It's real. It has plagued (no pun intended) certain vaccines, obvious for FIP but Dengue Fever vaccine is a similar but non-related example in humans.

I'll leave FIP alone now except for adding that work with the reagent GS-441524 suggests that FIP is no longer the invariable death sentence which it was two or three years ago. People who have worked clinically with FIP, or lost cats to FIP, will understand the awe that this drug inspires. I hope it gets used sensibly.

Anyhoo.

I was listening to Radio 4's The Life Scientific which featured an interview with Prof Sarah Gilbert from Oxford, heavily involved in the development of an adenovirus delivered vaccine for protection of humans against SARS-CoV-2.

Apart from how genuine and extremely bright she is the main thing I recall is her comment that she was very pleased that the vaccine she was developing produced a robust cell mediated immune response in additions to stimulating antibody production.

This is excellent and is all that you could ask of a vaccine where antibodies are frequently high and ineffective well before admission of patients destined to die of COVID-19 complications in the ITU.

It looks like cell mediated immunity is what matters. That antibodies are non protective is also suggested by the extremely poor results using antibody rich serum from recovered patients to treat unwell patients with COVID-19. There is no suggestion that serum treatment did direct harm, just it didn't do much good.

So the major question this poses is how much good the vaccine might do in patients who are going to become ill with COVID-19 in the future. It is not an unbelievable stretch of fantasy to suggest that the defining characteristic of people who are going to go on to become seriously unwell after exposure to SARS-CoV-2 might just be those are the ones who are unable to mount an effective cell mediated immune response.

How well might the T cells of an 80 year old, morbidly obese diabetic respond to the vaccine, assuming they are not very likely to respond to the field virus?

We can but hope that if they do fail to develop cell mediated immunity then at least their antibody response (which will still happen) does no harm. And we can hope that cell mediated immunity response has been carefully assessed in the population to which to a COVID-19 vaccine is being rolled out as of today in the UK... 

Otherwise it's a bit of an experiment on many, many people's grannies.

Peter