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Current Trends Antigenic Variation of Recent Influenza A(H3N2) Viruses

Analysis of recent influenza A(H3N2) viruses indicates antigenic drift from the previously prevalent strains A/Mississippi/1/85 and A/Leningrad/360/86. One reference variant virus strain, A/Victoria/7/87, was first isolated in Australia in April of this year. A second reference variant, A/Sichuan/2/87, was first isolated in China, also in April. In hemagglutination inhibition tests with antiserum from infected ferrets, antibody to A/Victoria/7/87 reacts poorly with other strains, even though the virus itself is inhibited well by antiserum to A/Mississippi/1/85 (Table 1). Antiserum to A/Sichuan/2/87 reacts at lower titers with viruses such as A/Mississippi/1/85 and A/Leningrad/360/86, which circulated earlier, than it does with A/Sichuan/2/87 antigen. Also, A/Sichuan/2/87 is inhibited poorly by antisera to all of the viruses that circulated earlier. Analysis of about 50 recently isolated A(H3N2) viruses from Asia, Oceania, and the United States indicates a spectrum of antigenic specificity, with many isolates having reaction patterns intermediate between A/Leningrad/360/86 and A/Sichuan/2/87.

The antibody response induced by the current type A(H3N2) vaccine component is greater toward the homologous A/Leningrad/360/86 virus than toward the reference variants A/Victoria/7/87 and A/Sichuan/2/87. This response confirms the existence of antigenic variation in recent virus isolates. Vaccinees in all age groups developed titers of 40 or more to A/Leningrad/360/86 with greater frequency than they did to the new antigenic variants (Table 2). In addition, the geometric mean titers were higher to the homologous A/Leningrad/360/86 antigen than to the antigenic variants A/Sichuan/2/87 or A/Victoria/7/87. Reported by: P Graves, G Meiklejohn, MD, School of Medicine, Univ of Colorado Health Sciences Center, Denver, Colorado. F Ruben, MD, Univ of Pittsburg, Pittsburg, Pennsylvania. P Palmer, K Edwards, MD, Vanderbilt Univ, Nashville, Tennessee. Influenza Research Center, Baylor College of Medicine, Houston, Texas. Participating State and Territorial Epidemiologists and State Laboratory Directors. Sentinel Physicians of the American Academy of Family Physicians. WHO Collaborating Laboratories. WHO Collaborating Center for Influenza, Influenza Br, Div of Viral Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: In 1987, the World Health Organization Collaborating Centers for Influenza (Atlanta and London), in conjunction with National Influenza Centers in several countries in Asia and Oceania, detected antigenic variants of influenza A(H3N2). Evidence is accumulating that these viruses are infecting persons of all age groups, including high-risk elderly persons (1). These variants are associated with the reappearance of influenza A(H3N2) viruses after a period of quiescence during the winter of 1986/87.

Antigenic variation has always complicated influenza vaccine formulation. The occurrence of viruses that exhibit antigenic drift from the vaccine strain has on occasion resulted in diminished vaccine efficacy, such as the failure of A/Port Chalmers/1/73 to protect against A/Victoria/3/75 (2). However, reduced vaccine efficacy has not always occurred in such situations. In 1972, vaccine containing A/Aichi/2/68 reduced cases of influenza by 60% in an outbreak caused by the antigenic drift variant A/England/42/72 (3), and, in 1977, A/Victoria/3/75 vaccine protected adults from A/Texas/1/77 infection with 80% efficacy (4). The mechanism of such cross (heterovariant) against A/Victoria/3/75 (2). However, reduced vaccine efficacy has not always occurred in such situations. In 1972, vaccine containing A/Aichi/2/68 reduced cases of influenza by 60% in an outbreak caused by the antigenic drift variant A/England/42/72 (3), and, in 1977, A/Victoria/3/75 vaccine protected adults from A/Texas/1/77 infection with 80% efficacy (4). The mechanism of such cross (heterovariant) protection is not precisely known. Although antigenic variants differ in some epitopes on the hemagglutinin, they also share other common hemagglutinin epitopes. Because type A(H3N2) viruses have circulated since 1968, most of the population has been primed by previously circulating strains and is, therefore, more responsive to heterovariant immunization. In addition, the antigenic changes described occurred in the hemagglutinin surface glycoprotein. Significant protection from illness may also be induced by the neuraminidase surface glycoprotein (5,6), which has shown less evidence of antigenic drift. Still other factors, such as the capacity of a strain to spread in the population, can emerge independently from changes in the antigenic properties of the hemagglutinin. Therefore, vaccine efficacy cannot be determined until placebo-controlled double-blind trials have been com pleted.

Nevertheless, laboratory studies, as well as preliminary observations during outbreaks of influenza A(H3N2) among high-risk residents of nursing homes, suggest that the A/Leningrad/360/86 component of the current vaccine may not provide optimal protection against presently circulating strains. These findings emphasize the need for health-care providers to be aware of the recommendations for use of the antiviral drug amantadine for controlling outbreaks and for prophylaxis or treatment of unprotected patients (7). Because amantadine, which is a prescription drug, must be given before exposure to prevent infection or within the first 1 or 2 days after onset of illness for treatment, contingency plans for its rapid use are needed. These plans include obtaining a physician's order to give the drug to high-risk patients at the first signs of influenza illness, knowing the precautions concerning dosage of the drug (particularly for persons with known renal insufficiency or with presumed reduced renal function, such as those over 64 years of age), and arranging for an adequate supply of the drug.

A fact sheet on amantadine, directed particularly at use in institutions caring for high-risk persons, is available through the Office of Public Inquiries, Centers for Disease Control, 1600 Clifton Road, NE, Atlanta, Georgia 30333.


  1. Centers for Disease Control. Update: influenza activity--United States. MMWR 1988; 37:49-50.

  2. Barker WH, Mullooly JP. Effectiveness of inactivated influenza vaccine among non- institutionalized elderly persons. In: Kendal AP, Patriarca PA, eds. Options for the control of influenza: proceedings of a Viratek-UCLA symposium held in Keystone, Colorado, April 20-25, 1985. New York: Alan R Liss, Inc, 1985:169-82.

  3. Stiver HG, Graves P, Eickhoff TC, Meiklejohn G. Efficacy of "Hong Kong" vaccine in preventing "England" variant influenza A in 1972. New Engl J Med 1973;289:1267-71.

  4. Meiklejohn G, Eickhoff TC, Graves P, I J (sic). Antigenic drift and efficacy of influenza virus vaccines, 1976-1977. J Infect Dis 1978;138:618-24.

  5. Monto AS, Kendal AP. Effect of neuraminidase antibody on Hong Kong influenza. Lancet 1973;1:623-5.

  6. Couch RB, Kasel JA, Gerin JL, Schulman JL, Kilbourne ED. Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J Infect Dis 1974;129:411-20.

  7. Immunization Practices Advisory Committee. Prevention and control of influenza. MMWR 1987;36:373-80,385-7.

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