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Despite considerable research efforts, little is yet known about key epidemiological parameters of H5N1 highly pathogenic influenza viruses in their avian hosts. Here we show how these parameters can be estimated using a limited number of birds in experimental transmission studies. Our quantitative estimates, based on Bayesian methods of inference, reveal that (i) the period of latency of H5N1 influenza virus in unvaccinated chickens is short (mean: 0.24 days; 95% credible interval: 0.099–0.48 days); (ii) the infectious period of H5N1 virus in unvaccinated chickens is approximately 2 days (mean: 2.1 days; 95%CI: 1.8–2.3 days); (iii) the reproduction number of H5N1 virus in unvaccinated chickens need not be high (mean: 1.6; 95%CI: 0.90–2.5), although the virus is expected to spread rapidly because it has a short generation interval in unvaccinated chickens (mean: 1.3 days; 95%CI: 1.0–1.5 days); and (iv) vaccination with genetically and antigenically distant H5N2 vaccines can effectively halt transmission. Simulations based on the estimated parameters indicate that herd immunity may be obtained if at least 80% of chickens in a flock are vaccinated. We discuss the implications for the control of H5N1 avian influenza virus in areas where it is endemic.

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SUMMARYTwo new monoclonal antibodies (MAbs) derived from mice immunized with the Pitman-Moore (PM) strain of rabies virus were used to identify and characterize two unique antigenic determinants on the rabies virus glycoprotein. One of the determinants, which defined an additional antigenic site on the rabies virus glycoprotein, was delineated as a distinct epitope by the newly generated MAb, 6-15C4, in competitive binding studies and by comparative antigenic analysis of neutralization-resistant variant viruses. Both antigenic determinants were compared with the five previously described antigenic sites which bind virus-neutralizing antibodies on the challenge virus standard (CVS) and Evelyn-Rokitnicki-Abelseth (ERA) strain glycoproteins. The results presented in this communication show that the 6-15C4 epitope is the first epitope described in the rabies virus glycoprotein that does not depend on the native conformation of the glycoprotein for binding virusneutralizing antibody. These data suggest that it may be possible to generate a synthetic peptide vaccine against rabies.INTRODUCTION Both humoral and cell-mediated immunity executed by antibodies directed against virus and antiviral T cell responses have been shown to contribute to the protection of animals against rabies virus infection ( Wiktor et al., 1974Wiktor et al., , 1977Turner, 1985). Previous studies have demonstrated that virus-neutralizing antibodies are induced solely by the glycoprotein of rabies virus (Wiktor et al., 1973(Wiktor et al., , 1984Cox et al., 1977). In addition, several CNBr cleavage fragments of the rabies virus glycoprotein have been shown to be capable of inducing virus-neutralizing antibodies (Dietzschold et al., 1982(Dietzschold et al., , 1983) and specific T cell responses . Studies of neutralization-resistant variant viruses selected in the presence of excess amounts of neutralizing monoclonal antibodies (MAbs) and competition binding assays using MAbs have provided evidence for at least three distinct antigenic sites on the glycoprotein of rabies virus in the challenge virus standard (CVS-11) strain and five in the Evelyn-Rokitnicki-Abelseth (ERA) strain (Lafon et al., i983, 1984). Many of these studies suggest that the virus-neutralizing antibodies preferentially recognize conformational epitopes derived from the secondary structure of the glycoprotein (Dietzschold et al., 1982;Wunner et al., 1985). In the present paper, we have further investigated the antigenic structure of the rabies virus glycoprotein, using additional MAbs recently generated in mice that were immunized with the Pitman-Moore (PM) strain of rabies virus. We present evidence for the existence of a novel conformationindependent antigenic determinant, which we have delineated as a separate antigenic site in the functional antigenic map of the glycoproteins of the CVS-11 and ERA rabies virus strains.

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