The insect based flu vaccine

The newswires are on it again. This one has a good hook. A flu vaccine made in insect cells. So I read the paper. And in truth, it's pretty interesting.

Genetically engineered flu vaccine made from yellow striped caterpillars instead of hen eggs has been shown for the first time to keep people from getting the flu, scientists say.

The results are preliminary but suggest the insect method could be a quicker, easier alternative to the lengthy, antiquated egg-based procedure now used and could lead to a more rapid response to a pandemic, the study authors say. (Lindsey Tanner, AP)

There's more to it than a new technology for producing flu vaccine. It's not the only non-egg based technology now. And this trial was actually done two years ago, in the 2004 - 2005 flu season. The method, splicing the gene for the hemagglutinin protein into an insect virus and then infecting the insect cells and inducing them to make protein, is somewhat faster than eggs (maybe a month), so that's good -- but not spectacular. DNA based vaccines could be deployed more quickly. But this paper, published as Preliminary Results in the Journal of the American Medical Association (JAMA), has shown a number of other things.

The JAMA paper reported a randomized controlled trial that included placebo injections, good follow-up for side effects and measurement of antibodies and unusually, some evaluation whether the vaccine actually protected against influenza, something that (fortunately) can't be done with current H5N1 vaccines. The new vaccine is an alternative to the current egg-based Trivalent seasonal flu vaccine meant to protect against two circulating strains of subtypes of influenza A (H1N1 and H3N2) and one of influenza B. By every measure -- although preliminary -- the new vaccine performed as well or better than the conventional vaccine prepared from virus grown in eggs. No more side effects, and none of them serious, and protection as full, at least in terms of antibody protection and protection against clinical illness. But the vaccine differs from conventional vaccine is more ways than how it was produced.

The fact that it did work is important because of these differences. The viral antigen here was different in several ways. First it represented only a single viral protein from each strain, the hemagglutinin (HA) protein. Conventional vaccines also include the neuraminidase (NA) protein and there has always been some question about the role of this NA component. It turns out that the H3N2 component of both the new and conventional vaccines was mismatched. The circulating strain was an A/California strain that cross-reacted poorly with the Trivalent and new vaccine, based on an A/Wyoming strain:

It has been suggested that the neuraminidase component of vaccine may be important for protection in situations in which there is not a close antigenic match in the hemaglutinin. The current study suggests that it is possible to generate a substantial amount of protection in an immunologically primed population against influenza with a pure hemagglutinin vaccine, even in the presence of significant antigenic drift. (Treanor et al., JAMA)

Thus we know something new about our response to vaccines and their ability to protect us. Antibodies to hemagglutinin are enough, even when there is a mismatch, or so it would seem (this assumes the prevented cases were also A/California, and although we don't know this for sure, it is quite likely). The hemagglutinin protein was also in the uncleaved form, HA0. When it is produced in insect cells its amino acid sequence is identical to the one produced in eggs and humans, but there are still differences in glycosylation, the pattern of sugars attached to the protein. It didn't seem to matter. This method produces substantial protein yields and the protein seems to be of good quality for immunological purposes. This has implications for other methods of producing immunogenic viral flu protein, including DNA based vaccines.

Even if this vaccine doesn't become the newest and best way to produce influenza vaccine, we've learned something. As I said, pretty interesting.


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"Mosura ya Mosura
Dongan kasakuyan Indo muu"
Mothra O Mothra
If we were to call for help...?

Revere, does each state have college or university labs that could be put to vaccine production, if one of the non-egg methods gets up to speed before pandemic does?
Would decentralizing vaccine production cause more problems, or solve a few?
Who has the "red tape scissors"?

By crfullmoon (not verified) on 12 Apr 2007 #permalink

crfullmoon; No. Vaccine production facilities are highly specialized and this kind of production even more so. I wouldn't want any facility but one that really knows how to do it to make vaccine. So I wouldn't count on this being something to save us at the last minute, a la the movie Outbreak. We learned something about vaccines from this trial and this is method that can produce much higher yields of viral antigen than eggs, so we are ahead a step or two from before. The intense work on vaccine technology that is now going on, given time, could soften the blow of a pandemic and given enough time, maybe even avert one. But for that to happen we would have to keep up the urgent pace of development and have at least a decade before the hammer falls, as well as work on incrasing overal global productive capacity and public health infrastructure so that even if a vaccine existed it could be administered.

There is no magic bullet. Forget it.

Not to mention the short lifespan of caterpillars, worms. Without a doubt some very interesting future stuff from this for things other than BF vaccine. They have proved they can make it, but on the other hand we might have to worry about long term problems from it too. Way down the road.

By M. Randolph Kruger (not verified) on 12 Apr 2007 #permalink

Wasn't looking for magic bullets (never saw that movie, don't watch many) just don't see my state able to meet its own needs and wondered how we could have an attempt at getting some local production.
I don't think we have another decade, (and I will be pleasantly surprised every 10 more months we do get).

I'd rather we were getting the public to think about coping with no vaccine in sight,
as that is more what we'll be having to do. ("Mr.Randolph's Neighborhood" is looking good, at this point.)(And, I'd swap MRK in and our face of ph in charge of our local "all-hazards" out, to get real Pandemic Preparedness started, anyday.)

By crfullmoon (not verified) on 12 Apr 2007 #permalink


This is my current personal favorite, as far as I can tell, for pandemic vaccine. I posted some of the reasons before…
and will add more here.

This particular study (I haven't seen the full paper) as you said is an older study, but the important thing for pandemic purposes is that at 45ug per antigen ie 135ug total, it is still very well tolerated. Because of the efficiency of production and production capacity, there is no need for dose-sparing strategies and adjuvants. The company's (it's a very small company) own capacity can produce 1 million doses of 135ug vaccine in 5 days (Cox, M, presented at conference). If you use the capacity of the many other biotech companies, it is feasible to make millions if not billions of doses within the timespan of the first wave of a pandemic.

It's faster not by a month, in a pandemic, but by 4-5 months because:

1) It can be manufactured from the genetic sequence only, not from virus seed samples, so you don't need to wait for the WHO process of making the RG seed strain that is safe for manufacturers. This cuts out maybe 10-12 weeks.

2) Production time from knowing the genetic sequence to product is 6 weeks.

Which means that realistically you can have a pandemic vaccine at 2-3 month after the onset of a pandemic, as opposed to 6-9 months.

The shorter production time also means you can continue to vary the antigen as the virus evolves, ensuring continuing good match to circulating strain with each new batch of vaccines.

Another benefit is it is made as you said from HA0, meaning that in the case of H5, it is based on the wild-type antigen, which should target the virus better, but without the biosecurity risk of actually working on the wild-type virus!

Since there are many of us out here who suffer not only from seasonal flu but from the aftereffects -- pneumonia, bacterial infections, asthma complications, etc. because of our EGG allergies, I think it is imperative that we get some non-egg based vaccines on the market ASAP. I for one, have been calling the CDC for over 20 years on this issue, since I am allergic to eggs. No one seems to think I and my other allergen-friends are enough of a population to even care about. We don't fall into the category of "orphans," but more into the category of "ignored." Let's get it done, folks.

By Susan Manola (not verified) on 02 Feb 2009 #permalink