Diffuse retinopathy following measles, mumps, and rubella vaccination.
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Biomedical subjects
Publications and source records attributed to D T Karzon.
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Peripheral blood lymphocytes were separated into several subpopulations and evaluated for their ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) against respiratory syncytial virus (RSV)-infected HeLa cells. Using erythrocyte rosetting methods, nylon wool filtration, and cytolysis with OKT-3 monoclonal antibody, two lymphocyte subpopulations were shown to mediate RSV-ADCC; non-T, non-B, and IgG-Fc receptor-bearing lymphocytes and E-rosetting cells with IgGFc receptors (T gamma cells). Removal of phagocytic cells did not alter ADCC activity. Monoclonal antibody to human NK and K cells, HNK-1, recognized these two lymphocyte effector subpopulations.
The three major immunocompetent cells in human peripheral blood (lymphocytes, neutrophils, and monocytes) were shown to be effector cells for antibody-dependent cell-mediated cytotoxicity (ADCC) against influenza virus-infected baby hamster kidney cells in vitro. Lymphocyte cytotoxicity was mediated by FcIgG receptor-bearing null cells and T gamma cells. These effector populations were best defined by HNK-1, a monoclonal antibody to human natural killer and ADCC-mediator cells. Antibody responsible for ADCC against influenza virus-infected cells was detectable in sera of young children after natural infection and after vaccination with inactivated and live attenuated viruses. ADCC antibody appeared before hemagglutination-inhibiting antibody and persisted for at least one year after vaccination with live attenuated vaccine. ADCC antibody was subtype-specific but quite broadly reactive within a subtype. Both hemagglutinin and neuraminidase were antigenic determinants for ADCC antibody. An anamnestic response to the original strain was observed after challenge with influenza virus of a heterologous subtype.
An intranasal, inactivated trivalent influenza A vaccine containing 7 micrograms of A/Bangkok/1/79 (H3N2) hemagglutinin was administered to 20 children aged 1 to 6 years to assess the local and systemic immune responses to antigen delivered to the respiratory tract. Six children without prior influenza virus infection exhibited no local immune response and manifested only a minimal systemic response to the intranasal vaccine. In contrast, five individuals who were previously infected with a live attenuated influenza A H3N2 virus vaccine, although having no residual secretory antibody at the time of challenge, promptly developed a local antibody response to intranasal, inactivated antigen. Therefore, the live influenza A virus vaccine had induced memory in the local immunoglobulin A (IgA) immune system. The third group of nine children had previously been infected with wild-type H3N2 influenza virus. A majority of these children had residual local and systemic antibody at the time of challenge but they demonstrated some boosting of local IgA antibody with administration of intranasal inactivated vaccine. The competence of the secretory IgA immune system in young children in mounting primary and secondary responses to influenza antigens has important implications for approaches to prevention of influenzal illness.
Cord blood lymphocytes, monocytes, and neutrophils from newborns were shown to mediate antibody-dependent cellular cytotoxicity (ADCC) against influenza virus-infected cells. Antibody mediating ADCC was detectable in cord plasma, indicating that all components necessary for ADCC against influenza virus-infected cells are present in newborns. Among adult lymphocytes, two effector cell populations of influenza ADCC are recognized: non-T and T gamma cells. Each of these cell types expresses an antigen recognized by monoclonal HNK-1 antibody. The proportion of HNK-1 antigen-positive lymphocytes in cord blood was markedly lower than in adult blood; furthermore, ADCC was mediated by cord blood lymphocytes which were HNK-1 negative. By lymphocyte fractionation, the effector lymphocytes in cord blood were, as in adults, non-T and T gamma cells, suggesting that HNK-1 antigen is not expressed on these cell lineages in newborns.
Two live, attenuated, intranasally administered influenza virus vaccines were evaluated in 21 seronegative young children at Vanderbilt Children's Hospital (Nashville, Tennessee). The vaccines were derivatives of a cold-adapted master strain, influenza A/Ann Arbor/6/60 virus, containing the hemagglutinin and neuraminidase of one of two contemporary strains, influenza A/Hong Kong/123/77 (H1N1) or A/Alaska/6/77 (H3N2) virus. Both vaccine strains replicated in seronegative young children without evidence of genetic instability. In addition, both vaccine strains caused no identifiable clinical reactions, were not transmitted to other seronegative children, and gave long-lasting immunity. In a subsequent naturally occurring epidemic of influenza A/Bangkok (H3N2) virus, children previously vaccinated with the related strain, influenza A/Alaska (H3N2) virus, were significantly protected as judged by serologic evidence of reinfection.
Three hundred one episodes of fever greater than or equal to 103 F were documented in 375 infants and young children observed in a comprehensive care clinic during the period October 1974 to October 1978. Of such highly febrile illnesses 79% were accompanied by respiratory tract signs or symptoms, 7% by disease at a site other than the respiratory tract, and 22% of illnesses had no localizing signs or symptoms. Viral cultures were obtained from the respiratory tract in 178 cases and were positive in 68: 57/134 from respiratory illness; 2/4 from illness at sites other than the respiratory tract; and 9/40 in children without localizing disease. Bacterial cultures of the upper respiratory tract were obtained in 191 illnesses, but the overall rate of isolation of Haemophilus influenzae, Streptococcus pneumoniae and group A streptococci (46%) did not differ from that in a group of well children (39%). Bacterial cultures of the blood were obtained in 89 patients with fever greater than or equal to 103 F and in an additional 41 children with lower temperatures. Nine children had documented systemic bacterial disease (eight positive blood cultures and one positive CSF). The rate of clinically apparent systemic bacterial disease in these otherwise normal infants was one bacteremic episode per 94 years of child care.
An influenza B/Hong Kong viral epidemic was monitored by surveillance of respiratory illness in three different age groups. Prospective viral monitoring of febrile respiratory illness was a useful mirror of the epidemiologic behavior of influenza in the community. Influenza B virus infection in infants and young children was distinguished by high fever and respiratory symptoms and was occasionally associated with otitis media. In older children and young adults, systemic and gastrointestinal complaints were more prominent. Of young children experiencing their first infection, a hemagglutination-inhibiting antibody response was seen in only one-third. Eleven children who received inactivated B/Hong Kong virus vaccine three years earlier were not protected from clinical infection but exhibited an anamnestic serum antibody response.
Sequential influenza A/Texas/77 (H3N2) and A/USSR/77 (H1N1) epidemics occurred during the winter of 1977-1978 in two populations under viral surveillance for influenza. In college students who reported to the Vanderbilt student health service, roughly equivalent amounts of typical influenzal disease were documented by virus isolation and total health service visits with both strains. However, considering that the college population was fully susceptible to the first introduction of H1N1 virus in 20 years and partially immune to H3N2 viruses through repeated exposure, A/USSR appeared to be a relatively less pathogenic strain. Stronger proof of this was seen in a closely monitored group of 200 largely seronegative infants and young children less than 4 years of age enrolled in an experimental vaccine clinic. In this young population, A/USSR caused no recognizable illness and A/Texas caused typical febrile respiratory disease. Thus, two influenza strains circulating in close temporal association differed in virulence when observed in carefully monitored susceptible populations.
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To assess the impact of an influenza A/Port Chalmers infection on normal young children, we monitored 147 children during an epidemic; 121 were seronegative. There was a high attack rate (61 of 147), and a high rate of symptomatic disease (38 of 147), which resulted in frequent physician visits (25 of 38). Influenza accounted for 76 per cent of the sick-child visits during the two-month epidemic period. Young children undergoing primary influenza infection produced hemagglutination inhibition and antineuraminidase antibodies. Because of the immunologic responsiveness of young children, we examined the serologic correlates of protection. Ten children previously infected with influenza A/London and 16 who received live, attenuated A/Hong Kong ts-1[E] vaccine were protected against infection with the non-homologous A/Port Chalmers strain. The morbidity of influenza and ability of the young child to produce protective antibody should encourage evaluation of life, attenuated influenza vaccines in this age group.
Paralytic poliomyelitis was observed in a child with a sex-linked defect in immunoglobulin synthesis. Evidence is presented that this was secondary to administration of oral, live poliovaccine. The demonstration of a familial sex-linked gammaglobulin deficiency and the failure to document a defect in cell-mediated immunity in this child extends the risk of vaccine associated poliomyelitis to virtually all forms of immunodeficiency. The critical host factors in the pathogenesis of poliovirus vaccine infection and in particular its unfavorable outcome appear to include either a deficiency in the humoral (B cell) system or in the cell-mediated (T cell) system.
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The total multicenter data from trials with inactivated monovalent influenza A/New Jersey/76 virus vaccine in 2,326 normal children were collected and summarized at Vanderbilt University (Nashville, Tenn.). These combined data provided the best measure of the relative antigenicity and reactogenicity of each manufacturer's vaccine. Children younger than 10 years of age were shown to have vaccine-associated reactions to doses of whole-virus vaccine containing as little as 50 chick cell-agglutinating units. Split-virus vaccines were well tolerated in doses eight times as high. No vaccine was satisfactorily antigenic in a single dose. A two-dose regimen of split-virus vaccine was antigenic, and this regimen was not associated with acute reactions.