Vaccine Virus for Novel H3N2 based on 2010 Swine Flu Strain

December 7, 2011 — 

The Centers for Disease Control and Prevention (CDC) got a head start on preparing a vaccine against the novel swine-origin influenza strain recently found in 4 states by using a slightly different swine-origin strain that cropped up last year, CDC officials said today. Since early September, the CDC has reported 10 infections with a swine-origin H3N2 reassortant strain that includes the M gene from the 2009 pandemic H1N1 (pH1N1) virus. The cases include: 2 in Indiana, 3 in Pennsylvania, 2 in Maine and, most recently, 3 in Iowa. 9 of the 10 recent cases have been in children; all the patients recovered. The Iowa cases were believed to involve person-to-person transmission, since the children attended the same daycare center and none of them had any exposure to pigs. The other 7 cases all had direct or indirect exposure to swine. On November 22, 2011 the CDC reported that it had prepared a vaccine virus and was providing it to vaccine manufacturers as a precaution in case the novel virus spreads.

A recent flu update from the World Health Organization (WHO) revealed that the vaccine virus is based on an isolate that was collected in Minnesota in 2010. A CDC official told CIDRAP News that the isolate is from a pair of swine-origin H3N2 infections that occurred in Minnesota in November 2010. Those cases were among 5 swine-origin H3N2 cases reported in 3 states during the 2010-11 flu season. The 2010 strain is not an exact match for the recent novel H3N2 isolates, but it is close enough to be the basis for a vaccine, said Michael Shaw PhD, associate director for laboratory science in the CDC's Influenza Division. "Since we were seeing these cases popping up sporadically, over the summer the decision was made to go ahead and try to make a high-yield reassortant [for a vaccine], and it turned out to be a good decision, to have it in reserve," Shaw said.

He said it takes several weeks to prepare a flu vaccine virus. In the case of the 2009 pandemic, the task took about 6 weeks, from April 15 to the end of May, which was considered fast, he noted. The reason the Minnesota isolate was chosen was that it was the only one available at the time that grew in eggs, Shaw explained. "Vaccine strains need to be egg-derived, because inactivated vaccines are grown in eggs," he said. "This one from November 2010 is not like the new reassortant in that it doesn't have that M gene from the H1N1 strain. But the HA [hemagglutinin] is close enough to be a good vaccine match."

Hemagglutinin is the viral surface protein that is recognized and targeted by the human immune system. The protein often mutates, making it necessary to formulate new vaccines. Shaw said the hemagglutinin of the 2010 isolate is very closely related to the version found on the recent swine-origin viruses. "We've characterized it genetically and antigenically, so it would be an acceptable vaccine strain, which is why we decided to distribute it to the manufacturers, so they can get some experience with it and grow it, in case they have to scale up."

To make a vaccine virus, the CDC first takes clinical isolates and puts them in eggs to see if they will grow, Shaw explained. Once an isolate that grows in eggs is identified, it is recombined with a laboratory strain that grows well in eggs. That task is handled by a separate lab at New York Medical College. The desired product is a "high-yield reassortant": a virus with internal genes from the lab strain and surface genes from the clinical isolate.

After a high-yield reassortant is obtained, it must be characterized to make sure it hasn't changed too much in the course of the lab manipulations, Shaw said. "There's a great deal of consultation with the FDA [Food and Drug Administration] and the WHO to reach the conclusion that it is the best one for its purposes," he added. "So about 6 weeks for the pandemic one, that's a very good timeline."

Since the creation of the vaccine virus from the 2010 isolate, the CDC has succeeded in growing one of the more recent novel H3N2 viruses, from an Indiana case, in eggs, but "we don't have a high-yield reassortant available for it," Shaw said. "For now the Minnesota one is the only one that's egg-derived and for which we have a high-yield reassortant."

Source: CIDRAP News [edited] By Robert Roos