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1、The Time Course of the Immune Response to Experimental Coronavirus Infection of Man Author(s): K. A. Callow, H. F. Parry, M. Sergeant and D. A. J. Tyrrell Source: Epidemiology and Infection, Vol. 105, No. 2 (Oct., 1990), pp. 435-446 Published by: Cambridge University Press Stable URL: http:/www.jsto
2、r.org/stable/3864013 . Accessed: 18/06/2014 18:57 Your use of the JSTOR archive indicates your acceptance of the Terms Callow, unpublished observations. The method used to establish a significant rise in serum specific IgG has been described previously 12, 22. Paired sera from 14 volunteers who rece
3、ived intranasal saline instead of virus were tested for specific IgG as described above. A significant rise was set as the mean difference between these paired sera plus two standard deviations, i.e. 0*14 log10 units in this study. Statistical methods The analysis was performed on an IBMXT computer
4、using the program, Statistical Package for Personal Computers (SPP) written by Patrick Royston of the Clinical Research Centre. To examine the difference in antibody concentration on different days, in particular on any day compared with the pre-challenge value, and to compare antibody concentration
5、s in infected and uninfected volunteers, t- tests were used. Treatment of missing values There were a few instances when samples were not available for investigation. In these cases, for the graphical representation of results, an estimate ofthe value of single missing samples was obtained by interp
6、olation from the value of the samples taken just before and after the missing ones. This estimate was not used for statistical analysis. Field study Serological response to natural coronavirus infection was investigated by testing sera obtained in a field study of influenza prophylaxis described els
7、ewhere 19. Briefly, this involved military personnel volunteers who were given either influenza vaccine, amantadine (during influenza epidemics) or placebo prophyl- actically. Respiratory tract illnesses were recorded over a 3-year period, and infections with common respiratory viruses diagnosed by
8、isolation from nose or throat swabs, and/or by seroconversion. Serum samples were obtained at the beginning of the study, at 4-6 week intervals thereafter, and in the acute and convalescent stages of any respiratory illness. RESULTS Preliminary trials Neutralizing antibodies and specific IgG and IgA
9、 in sera were monitored during and after infection with coronavirus 229E in 16 volunteers on standard 10-day trials. Although concentrations of all three types of antibody were significantly raised in sera taken about 3 weeks after inoculation, by 12 weeks the concentrations had fallen considerably.
10、 Fig. 1 shows these effects in six volunteers This content downloaded from 195.34.79.208 on Wed, 18 Jun 2014 18:57:50 PM All use subject to JSTOR Terms and Conditions Immune response to coronavirus infection 34 j (a) 3-2- n 3? S 1 2-8 H S i 8 2 2-6 439 2 C/3 1 3 24 2-2 J 12 10 6J (Pre) 3 Weeks after
11、 inoculation Fig. 1. Changes in concentration of serum antibodies (geometric mean) of six volunteers infected with coronavirus 229E in preliminary trials. Bars represent the standard error of the mean. (a) Specific IgG ?-#; Specific IgA #-#. (b) Neutralizing antibody titres. from whom serum samples
12、were also available 1 year later. By this time mean antibody concentrations were only slightly higher than those measured before the trial. There were considerable individual differences however. Two volunteers had retained high concentrations of specific IgG, the others had returned to their baseli
13、ne values or just above. With this preliminary information extended trials were planned to obtain details of changes in both serum and nasal antibody in the first 3 weeks after virus inoculation as well as long-term changes. Extended trials (a) Infection and illness resulting from coronavirus inocul
14、ation Of 15 volunteers inoculated with coronavirus, 10 became infected as indicated by virus shedding on at least 1 day. All of these also had a significant rise in serum specific IgG. Eight of the 10 infected volunteers had clinical colds of varying severity. For the purposes of this study the volu
15、nteers were divided into two groups, an infected and an uninfected group. (b) Changes in total blood lymphocytes The mean total lymphocyte count before challenge was higher in the infected group than the uninfected group, although this difference was not statistically significant (Table 1). In the infected group there was a significant decrease in This content downloaded from 195.34.79.208 on Wed, 18 Jun 2014 18:57:50 PM All use subject to JSTOR Terms and Conditions 440 K. A. Callow and others Table 1. Mean concentration ( x 109/l) of total
