Originally Posted by
rsvman
I read through the article. I didn't think it was that bad, actually. The person they quoted about potential for misted live-virus vaccine is a friend of mine I used to work with at Vanderbilt many years ago. She is an influenza expert. Many of the trials that allowed FluMist to go to market were carried out at Vanderbilt by a team that included her, Bill Gruber, Peter Wright, and others.
FluMist was never dangerous. At all. Period.
When thinking about live attenuated vaccines, there are a few things of importance; perhaps the most crucial point was not mentioned in the article (Dr. Neuzil probably thought it was too complex for a lay article) and that is this: How stable is the attenuation?
Once you put a live, replication competent vaccine virus into a human body, it replicates. Virus can make many, many copies of themselves. In some past vaccines, with multiple rounds of replication the attenuation would go away, yielding a wild-type virus. This was case, for example, with oral polio vaccine. Oral polio vaccine attenuation was actually highly unstable. It reverted to wild type virus with alarming frequency. It was also spread very easily in the community, which actually helped contribute to herd immunity (even "unvaccinated" people were getting vaccinated!). The good news was that even wild type polio infection was benign in the vast majority of people who contracted it. Thus, we were able to get away with using an unstable vaccine for many years, and achieving herd immunity by having the vaccine spread all over the community. Babies and children vaccinated with oral polio vaccine would shed it in their stools for weeks to months. Because of this, for many years we had small numbers of children getting what was known as "VAPP" (vaccine-associated paralytic poliomyelitis), generally between 3 and perhaps 10 or 11 kids per year in the U.S., averaging about 5 or 6 per year. I actually took care of one of these kids when I was at Vandy. This is the reason that we moved away from oral polio vaccine and now exclusively use the injectable vaccine (which is not live).
On the other hand, we have been using live measles, mumps, rubella, and varicella vaccines for long periods of time without any real problems.
Back to FluMist. There is a lingering belief that the vaccine could be spread to others, but there have been no reliable case reports of this. The original studies looking at the potential for spread were done in daycare centers, to maximize the chances that spread would occur. They gave half the toddlers in the daycare the vaccine. They did nasal samples for vaccine virus every day in every kid, looking to see how long it was shed and whether it would spread. The official report of the research says that there was one child who did not receive vaccine who developed infection with the vaccine virus, but in truth it was probably a labeling error. Kid A, who got the vaccine, tested, on consecutive days, positive, positive, positive, negative, positive, positive. Kid B, who did not receive vaccine, tested, on consecutive days, negative, negative, negative, positive, negative negative. So on that one day, the vaccinated child suddenly stopped shedding for one day, but started up again the next? And the unvaccinated kid, supposedly infected with the vaccine virus, shed it for only one day and then cleared it? And that day just happened to coincide with the day the vaccinated kid cleared it transiently? Yeah, right. The samples were labelled incorrectly (in my opinion). So, bottom line, even toddlers in a daycare couldn't figure out how to share it with others. And, the attenuation was incredibly stable.
The reason FluMist fell out of favor was not because it was dangerous but because there was a problem that led to inefficient protection from H1N1 for one season. The problem was solved by the company by the next year, but by then the horse was out of the barn.
It is not at all clear to me that a live attenuated vaccine misted up the nose would be superior to other forms of vaccines for SARS-CoV-2, although the argument could be made that allowing a replication-competent vaccine virus to replicate generally produces a broader response, usually including some T-cell responses to internal proteins, which could be helpful as most viral mutations take place in the outer proteins.
What was I talking about? Oh yeah, live attenuated viral vaccines. So, the next concern is will the vaccine produce immunity without making the recipient ill? That's a fine line to walk; attenuate the virus too much and it will be tolerated fine but not produce significant immunity. Attenuate it not enough and it will make people sick.
Finally, will it be spread to others? The general public would see spread as bad, and it probably mostly is, because if we had a live virus vaccine we would not give it to people who are severely immune suppressed. If it spread around readily we could not control who would get "vaccinated," and that could lead to disastrous consequences.
Sorry if this was too long. Talk about walking a fine line...if I gloss over stuff too much it won't have any meaning but if I go too deeply into it, nobody will want to read it and/or it will be really difficult to understand. I hope this was on that line, providing information that is understandable and helpful without being overly technical and ridiculously boring.
