Influenza type A viruses undergo two major kinds of changes. One is a series of mutations that occurs over time and causes a gradual evolution of the virus. This is called antigenic "drift." The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic "shift." In this case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift and therefore do not cause pandemics.
Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. Sensitivity and positive predictive value of clinical definitions vary, depending on the prevalence of other respiratory pathogens and the level of influenza activity in the community. Among generally healthy older adolescents and adults living in areas with confirmed influenza virus circulation, estimates of the positive predictive value of a simple clinical case definition of influenza (acute onset of cough and fever) for laboratory-confirmed influenza virus infection have varied (range: 79%--88%) ( 80--82 ).
We have previously shown that a pulmonary influenza virus infection in SCID mice can be cured by treatment with monoclonal antibodies (MAbs) specific for the viral transmembrane protein hemagglutinin (HA) but not for matrix 2. Since both types of MAbs react with infected cells but only the former neutralizes the virus, it appeared that passive MAbs cured by neutralization of progeny virus rather than reaction with infected host cells. To prove this, we selected a set of four HA-specific MAbs, all of the immunoglobulin G2a isotype, which reacted well with native HA expressed on infected cells yet differed greatly (>10,000-fold) in virus neutralization (VN) activity in vitro, apparently because of differences in antibody avidity and accessibility of the respective determinants on the HA of mature virions. Since the VN activities of these MAbs in vitro were differentially enhanced by serum components, we determined their prophylactic activities in vivo and used them as measures of their actual VN activities in vivo. The comparison of therapeutic and prophylactic activities indicated that these MAbs cured the infection to a greater extent by VN activity (which was greatly enhanced in vivo) and to a lesser extent by reaction with infected host cells. Neither complement- nor NK cell-dependent mechanisms were involved in the MAb-mediated virus clearance.