Two recent papers reported on strong immune responses to different flu strains; in one case, this is good news, and in the other, not so much.

In a paper published online in Nature Sept. 27, 2006, scientists reported that when mice were infected with the reconstructed 1918 pandemic influenza virus, the result was the worst of both worlds: Although the infection triggered a very strong immune response, that response did not protect the animals from severe lung disease and death, and may have in fact been a contributing factor to their demise.

The scientists also noted that the 1918 virus appears to have been the viral equivalent of a perfect storm. Their results, they wrote, are "in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes."

If that report gives little comfort to those simultaneously trying to head off a new pandemic flu and planning for ways to contain its effects if prevention efforts fail, a new paper on vaccine development bears rather better news. In a paper that is slated for the Nov. 1, 2006, issue of Clinical Infectious Diseases, now available online, researchers at Baylor College of Medicine in Houston reported on an adjuvant that leads to an effective immune response to an avian influenza vaccine with doses as low as a quarter of what is necessary without the adjuvant.

The Nature paper was published by scientists from the Mount Sinai School of Medicine in New York City, the University of Washington School of Medicine in Seattle, the Centers for Disease Control and Prevention in Atlanta, and the Armed Forces Institute of Pathology in Bethesda, Md. The researchers compared mice infected with the reconstructed 1918 influenza virus to a control group infected with a currently circulating human influenza strain.

The mice infected with the 1918 virus showed a rapid and potent immune system response, but it didn't do them any good: The animals also developed severe lung disease, and most died within five days of infection. Control animals developed a more moderate immune response and had a lower death rate.

Gene expression studies on tissue samples from the lungs of infected animals showed that mice infected with the reconstructed 1918 strain had stronger activation of pro-inflammatory and apoptotic pathways. The scientists concluded that activation of those genes "might be contributors to severe immunopathology associated with [reconstructed 1918] influenza virus infections," although they cautioned that "it is not possible to completely exclude the possibility that increased immune and cell death responses may be a consequence rather than the cause of enhanced pathology of infection" with the virus.

The Clinical Infectious Diseases study reported on an adjuvant, MF59, which is approved for use in Europe but not the U.S. In a clinical study, MF59 was effective in boosting the antibody response to flu vaccine at each of four vaccine doses tested; four and eight weeks after vaccination, subjects that were vaccinated with one dose of vaccine-adjuvant combination showed an antibody response that was equivalent to two doses of vaccine without adjuvant.

The investigators used the H9N2 influenza strain for their research, which is itself a pandemic threat, though not one that has received as much attention as the H5N1 strain. Like H5N1, the H9N2 now circulates mainly in birds, and humans have little to no cross-immunity from other flu strains, meaning that H9N2 could spread very rapidly if it acquired the capacity for human-to-human transmission. In 1999 and 2003, a total of three cases of H9N2 were reported in Hong Kong; as a result, in 2004 the National Institutes of Health asked Chiron Corp., of Emeryville, Calif., to produce 40,000 doses of vaccine against the H9N2 strain.

Some of those doses were made with MF59. Other companies working on flu vaccines that could provide protection against the H9N2 strain include Malvern, Pa.-based Novavax Inc.; AVI BioPharma, of Portland, Ore.; and Crucell NV, of Leiden, the Netherlands.