After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.

SUMMARYThirty-three volunteers were inoculated intranasally with coronavirus 229E, and their responses monitored by antibody rises, symptomatology and virus excretion. These were related to their pre-trial immune status as indicated by concentrations of specific antibodies and non-specific proteins in serum and nasal washings. Both circulating and local specific antibodies were associated with protection from infection and disease, but only specific IgA antibodies of either type appeared to shorten the period of virus shedding. Although total secretory IgA was significantly associated only with reduction of symptoms, total protein in nasal washings appeared to protect against infection also, indicating that other locally produced proteins, not identified, may be associated with resistance.Two of the many factors which may affect the concentration of circulating and local protective proteins and thus influence the outcome of virus inoculation, namely, sex of the volunteer and the interval since the previous cold, were examined. Male volunteers or volunteers who had had evidence of a recent respiratory infection were less likely to be infected, but if they were infected, they had lower clinical scores and stopped shedding virus earlier than the rest. These groups possessed higher concentrations of specific antibodies and non-specific proteins in their pre-challenge sera and/or nasal washings. The significance of these findings is discussed.

A simple method of assaying anti-influenza neuraminidase antibodies in human sera was described. Suitable antigenic hybrid viruses were adsorbed to sheep erythrocytes, which were then incorporated into agarose gels. When sera were introduced into wells cut in the gels, zones of hemolysis were observed in the neighborhood of those containing neuraminidase antibodies. There was a direct relationship between zone size and antibody titer. No purification of adsorbed viruses was necessary. The test was rapid, required very simple reagents, gave results that agreed well with those given by conventional techniques, and appeared to be the most sensitive of four methods evaluated. Studies of cross-reactions by hyperimmune sera against homologous and heterologous neuraminidases and of absorption of neuraminidase antibodies from human sera indicated a high degree of specificity. The technique seems to be suitable for large-scale epidemiological investigations.

Summary In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty‐four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty‐nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P < 0.01). A similar association was found between clinical scores and serum IgE concentrations 150 IU/ml, but the relationship with systemic atopy, as assessed by skin‐prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast ceil mediator release, as concentrations of leukotriene B4, the sulphidopeptide leukotriene C4, and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggests that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.

A new study is described of the use of single radial haemolysis (SRH) for the measurement of antibodies to influenza virus neuraminidase (NA). The technique is known to be consistently successful in the assay of anti-haemagglutinin (HA) antibodies, subject only to the condition that the indicator virus belongs to an appropriate serotype. Its adaptation to the measurement of anti-NA is, however, more difficult. The virus used must be a recombinant which contains a specific NA and an "irrelevant" HA. However the present experiments showed that the two recombinants MRC-3 and X-38, which contain the same NA but a different HA, gave different results. Other properties of recombinants, including rates of attachment to and elution from red cells, may affect the results. The chemical NA-inhibition test (NI), although requiring the use of antigenic hybrids, did not produce these discrepancies. However it appears possible to exploit the simplicity and convenience of SRH for mass survey of anti-Na, if individual hybrid recombinants can first be shown to yield results comparable to those obtained by NI.