Immunogenic Recombinant Flu Vaccine Incubated in Insect Cells

ROCHESTER, N.Y., April 10 -- A genetically engineered seasonal flu vaccine incubated in insect cells, rather than chicken eggs, is safe and produces a robust immune response, researchers here have found.

The vaccine, which includes recombinant proteins from three strains of influenza, also appears to protect against the disease, according to John Treanor, M.D., of the University of Rochester.

The finding may offer a way around the major bottleneck in flu vaccine production -- the need to grow the vaccine in chicken eggs, Dr. Treanor and colleagues reported in the April 11 issue of the Journal of the American Medical Association.

The use of eggs to grow the annual flu vaccine has several well-known disadvantages, particularly an inability to scale up rapidly in response to epidemic or pandemic conditions, they said.

On the other hand, the influenza protein hemagglutinin can be easily and quickly grown in insect cells using a recombinant baculovirus - dubbed rHA0 -- modified to express the protein.

In the 2004-2005 flu season, Dr. Treanor and colleagues conducted a randomized, placebo-controlled trial of a vaccine consisting of recombinant hemagglutinin proteins from two influenza A strains and one influenza B strain.

The strains used were the same as the ones in the standard trivalent vaccine for the year, Dr. Treanor and colleagues said, and included an H1 hemagglutinin, and H3 hemagglutinin, and the hemagglutinin from influenza B.

For the study, 460 healthy adult volunteers were randomized to get placebo or one of two doses (75 or 135 mcg) of the recombinant rHA0 vaccine. The main endpoints of the study were safety and immunogenicity, defined as at least a fourfold increase in antibodies to the hemagglutinin proteins.

The study found that volunteers getting either vaccine dose had significantly more pain and tenderness at the injection site (at P<0.001 and P=0.04, respectively) than did those getting placebo, but no other significant differences in adverse events.

Among volunteers getting placebo, 3% had a fourfold antibody increase to the H1 hemagglutinin, 11% to the H3 hemagglutinin, and 4% to the influenza B hemagglutinin.

In contrast:

• 51% of volunteers getting the 75-mcg vaccine had a fourfold antibody increase to the H1 hemagglutinin, 81% to the H3 hemagglutinin, and 65% to the influenza B hemagglutinin.
• 67% of volunteers getting the 135-mcg vaccine had a fourfold antibody increase to the H1 hemagglutinin, 77% to the H3 hemagglutinin, and 92% to the influenza B hemagglutinin.

Although both doses of the vaccine produced acceptable levels of immune response, Dr. Treanor and colleagues said, the higher dose did better and should be pursued in trials comparing it to the standard trivalent flu vaccine.

Because of the small number of volunteers, the study had only a limited ability to detect efficacy, the researchers said, but there was some evidence that it worked to protect against disease.

There were 13 positive cultures for influenza in the study population, including seven of 153 placebo recipients (4.6%), two of 150 (1.4%) recipients of the 75-mcg vaccine, and, and none of the 151 volunteers who got the 135-mcg dose.

If both vaccine groups are considered together, Dr. Treanor and colleagues said, the "cumulative incidence of culture positive CDC-defined influenza-like illness was reduced by 86%" compared with placebo. The reduction compares well to the efficacy of the standard trivalent vaccine, they said.

"The preliminary demonstration of protective efficacy in adults provides further support for the development of this promising approach for prevention of seasonal and pandemic influenza," the researchers concluded.