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.