RESUMO
Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotoxin and play a role in the pathophysiological mechanism whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to stimulate a humoral immune response was examined in naturally infected children and adults, rotavirus vaccinated children, as well as a cellular immune response in adults. In this study, 10 of 10 naturally infected children and 9 of 10 rotavirus-vaccinated children showed a weak humoral IgG immune response to recombinant NSP4 (rNSP4) and/or a synthetic peptide corresponding to residues 114-134 of NSP4. Modest serum IgG antibody responses were detected in 20 of 20 adults. A cellular immune response to rNSP4 and/or NSP4(114-134) were detected in 8 of 10 adults measured either as a T-cell proliferative response (7 of 10), an increased production of IL-2 (6 of 10), or increased production of interferon-gamma (8 of 10). These results indicate that NSP4 induces a humoral immune response in humans and show for the first time that NSP4 stimulates a cellular immune response, possibly including cytolytic T-cells.
Assuntos
RNA Polimerases Dirigidas por DNA , Infecções por Rotavirus/imunologia , Rotavirus/química , Proteínas não Estruturais Virais/imunologia , Adulto , Anticorpos Antivirais/sangue , Finlândia , Humanos , Imunidade Celular/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Lactente , Nicarágua , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Rotavirus/imunologia , Infecções por Rotavirus/virologia , Suécia , Linfócitos T/metabolismo , Proteínas não Estruturais Virais/biossínteseRESUMO
In a randomized, double-blind, placebo-controlled trial, 331 infants aged 6 to 12 months received orally, at an interval of 1 month, either two doses of live attenuated bovine rotavirus vaccine strain RIT 4237 or equivalent placebo. The vaccinations were carried out during September to November, a non-rotavirus season; only three cases of rotavirus diarrhea occurred in the study group before the vaccinations were completed. During the epidemic season from December to May, 31 patients with clinically significant rotavirus diarrhea required therapy. Five of these were among the 168 vaccine recipients, and 26 among the 160 placebo recipients (P less than 0.001), giving a vaccine protection rate of 82%. The incidence of clinically significant diarrhea from all causes was reduced by 76% in the vaccinees. As determined by an enzyme immunoassay antibody test with homologous virus antigen, seroconversion after vaccination was obtained in 53% of the initially seronegative infants. Clinical protection correlated well with seroconversion, but the vaccinees who failed to seroconvert also had less rotavirus diarrhea than the placebo recipients, suggesting that immunity may be mediated by factors other than serum EIA antibody. Seventeen of the 23 rotavirus isolates in the epidemic season that were typed were of serotype 1, two were of serotype 2, and four were of serotype 3. The protection rates against clinically significant diarrhea were 72%, 100%, and 100% for serotypes 1, 2, and 3, respectively. We conclude that epidemic infantile winter diarrhea associated with human rotaviruses can be significantly reduced by vaccination with the live attenuated RIT 4237 bovine rotavirus vaccine before the epidemic season.
Assuntos
Infecções por Rotavirus/terapia , Vacinas contra Rotavirus , Vacinas Atenuadas , Vacinas Virais , Ensaios Clínicos como Assunto , Diarreia/terapia , Surtos de Doenças , Método Duplo-Cego , Humanos , Lactente , Placebos , Distribuição AleatóriaRESUMO
Serum IgA class reticulin antibody (RA) was found in 28 (97%) of 29 children with flat small bowel mucosa, and in low titer in four (2%) of 245 with normal or near normal mucosa on small intestinal biopsy. Thus the sensitivity of the IgA-RA fluorescent antibody test for screening of celiac disease was 97% and the specificity 98%. IgA-RA was superior to IgG-RA for the detection of celiac disease. During follow-up of patients receiving a gluten-free diet, the IgA-RA rapidly decreased and in most cases disappeared within a year, suggesting that the test may be useful for clinical follow-up of celiac disease as well.