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.
References
Centers for Disease Control. Update: influenza activity--United
States. MMWR 1988; 37:49-50.
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.
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.
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.
Monto AS, Kendal AP. Effect of neuraminidase antibody on Hong
Kong
influenza. Lancet 1973;1:623-5.
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.
Immunization Practices Advisory Committee. Prevention and
control
of influenza. MMWR 1987;36:373-80,385-7.
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