Epidemics of influenza have been recognized and fearedsince the 12th century. While anyone can be afflicted, thevery young and very old are most likely to develop severecomplications that can lead to death.

The viral connection for the flu has only been knownsince 1933. Influenza A is the viral strain that mostfrequently causes the flu with epidemics of this strainoccurring about every three years. Several variations ofeach flu strain exist with new ones constantly developing.These new variants are named for their presumed place oforigin, thus one year the Hong Kong flu emerges andanother year the Asian flu emerges.

Because the flu is caused by a virus, antibiotics areuseless against its onslaught and no effective treatmentexists. Protection by immunization is available, butcurrent vaccines are only moderately effective. Also,being immune to one viral strain variant does not protectone from others, and the immunity induced by vaccines isonly temporary.

In a recent Cooperative Research and DevelopmentAgreement announcement, the National Institute ofAllergy and Infectious Disease (NIAID) has made thetechnology for producing Influenza A vaccines that wasdeveloped in its labs available for licensing. Potentiallicensees will work with Brian Murphy, a viralimmunologist in the Laboratory of Infectious Diseases, todevelop his temperature sensitive mutants of thepolymerase basic 2 (PB2) protein gene into improvedcommercial vaccines for this most common flu strain.

Murphy and his colleagues have introduced temperaturesensitive mutations into the PB2 protein gene. Byintroducing viral RNA transcribed from these mutatedgenes and a helper virus into kidney cells from birds, thenormal PB2 protein gene from the helper virus can bereplaced by a mutant PB2 protein gene. As a result of themutations in the PB2 protein gene, the recombinedviruses are greatly weakened or attenuated, yet they cangrow efficiently in human cells.

By using this system, Murphy was able to introduce threeattenuating temperature sensitive mutations into the PB2protein gene and recover an infectious virus with thistriple mutant gene. The recombined virus bearing thismutant gene was highly attenuated, but genetically stableafter long-term growth in immunosuppressed rodents.Most importantly, the recombined virus was able toinduce immunological resistance to a normal or wild typestrain of influenza A virus.

Current flu vaccines consist of either inactivated virusesor semi-purified hemagglutinin or other disrupted virioncomponents. By using the NIAID technology, attenuatedviruses that contain the antigenic hemagglutinin andneuraminidase glycoproteins from newly emerged flustrains can be used to make vaccines.

As Michael Mowatt, a licensing officer in the TechnologyTransfer Office at NIAID, told BioWorld Today, "Themost important aspect of this technology is its ability torapidly introduce these attenuating mutations by geneticrecombination into new epidemic or pandemic variants ofinfluenza A as quickly as they emerge." He went on topoint out that using this recombination technology shouldhelp expedite the manufacture of vaccines against newlyarising variants.

Mowatt also explained that the NIAID technology is idealfor providing a supplement to the currently usedinactivated viral vaccines. He said, "These moreimmunogenic attenuated viruses can be deliveredintranasally, thereby giving a boost to local mucosalimmunity and eliciting a specific antibody response at thesite of viral entry in the nose and lungs."

Murphy said that the latter aspect of his work wouldprovide "more benefit to the very young and the veryold." These are the sufferers who are most at risk. AsMurphy explained, these are also the sufferers in whomthe current vaccines are most limited in theireffectiveness. n

-- Chester A. Bisbee Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.