A cell-culture–derived vaccine was 71% effective at protecting against seasonal influenza, according to results of a large randomized, controlled trial published online in the Lancet Feb. 16.
The study’s results "suggest that the Vero-cell–derived influenza vaccine is at least as effective in preventing culture-confirmed influenza infection as inactivated and live attenuated egg-derived vaccines," the study investigators said.
In addition, cell-culture vaccines might lead to more reliable vaccine supplies and better matches with prevalent influenza strains, they noted.
Only 23 of the 3,619 study participants (0.6%) who were given the vaccine during the 2008-2009 influenza season developed laboratory-confirmed influenza, compared with 80 of the 3,617 participants (2.2%) given placebo. The investigators calculated the vaccine’s protective efficacy to be 71.5% (Lancet; 2011 Feb. 16 [doi:10.1016/S0140-6736(10)62228-3]).
The protective efficacy was 78.5% against the three influenza strains contained in the vaccine, explained P. Noel Barrett, Ph.D., of Baxter BioScience (Orth/Donau, Austria), and colleagues.
Seasonal influenza vaccines are typically derived from embryonated hens’ eggs – a cumbersome practice with a host of manufacturing problems that often result in vaccine shortages. In contrast, vaccines derived from cell culture are made in standardized, closed manufacturing systems, allowing for a more reliable production process, the study’s authors noted.
The use of vaccines from cell culture might improve the effectiveness of seasonal influenza vaccines, the investigators said. With vaccines derived from hens’ eggs, investigators must make educated guesses on the influenza strains that will be prevalent more than 6 months into the future. With cell-culture–derived vaccines, however, predicted seasonal strains could be incorporated much closer to flu season.
Investigators recruited study participants at 36 centers in the United States between Dec. 1 and Dec. 15, 2008. The participants were healthy adults aged 18-49 years who received intramuscular injections either of a Vero-cell–derived, trivalent, inactivated-influenza vaccine or placebo. They returned to the clinics 18-24 days after vaccine for a blood draw to determine hemagglutination titres. At that time, participants were instructed to return once again within 48 hours of the onset of influenza-like symptoms. At those visits, investigators obtained nasopharyngeal swabs for culturing and typing viruses.
Adverse events associated with the vaccine tended to be mild or moderate. Among the vaccine recipients, 43% reported injection-site pain, compared with 8% of those receiving placebo. Other adverse events substantially more common in vaccine recipients were myalgia (18% vs. 6%), malaise (14% vs. 8%), fatigue, (18% vs. 12%), and headache (18% vs. 13%).
Compared with vaccines derived from embryonated eggs, vaccines derived from cell culture have several advantages, Dr. W. Paul Glezen of Baylor College of Medicine, Houston, wrote in an accompanying editorial (Lancet; 2011 Feb. 16 [doi:10.1016/S0140-6736(11)60174-8]).
"These advantages include availability and flexibility in use of tissue culture compared with the seasonality of use of hens’ eggs which, for the large quantities needed, must be scheduled in advance," Dr. Glezen explained. "Egg-based production processes are susceptible to microbial contamination, which has delayed vaccine production at some manufacturing sites in recent years."
In addition, some human influenza viruses such as subtype A H3N2 could be difficult to grow in eggs to generate the amount needed for vaccine production, he noted. And avian viruses such as subtype A H5N1 that are potential pandemic threats might prove lethal to chick embryos.
"The advantages of tissue-culture substrates allow a shorter production time between the annual determination of the vaccine’s formula and the distribution of vaccine," Dr. Glezen wrote. "The use of a tissue-culture substrate could shorten production time by 10 weeks, which might be crucial in a pandemic alert. Furthermore, production of vaccine antigens in tissue culture provides a safer vaccine for individuals who are allergic to eggs."
Dr. Glezen noted that the most important advantage of tissue-culture-grown influenza antigens might be the ability to preserve the structure of the hemagglutinin’s antibody-combining sites.
"Hemagglutinin is the most important surface antigen on the influenza virus, and protection is generally defined by the robustness of the antibody response to this antigen," he explained. However, adapting human influenza viruses to grow in the chick embryo alters the hemagglutinin antigen.
"Animal studies suggest that the use of vaccine virus antigens grown in mammalian cells could enhance protection after challenge with the human virus," Dr. Glezen said. "Also, the immune response might be broader than that produced by egg-grown antigens, which allows the possibility of better protection against new variants of prevalent viruses."
In addition, shortened production times would allow more time to make decisions about which influenza strains to include in influenza vaccines, he noted.
The DynPort Vaccine Company, with support from the U.S. government, funded the study. Two of the study authors hold patents on influenza vaccines derived from Vero-cell cultures. Six of the authors are employed by Baxter BioScience and have equity interests in the company. Two others are employed by DynPort, and one has an equity interest. Dr. Glezen disclosed serving as a coinvestigator for a grant funded by MedImmune Vaccines, and having received honoraria from AstraZeneca.