A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalence has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%-41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that H. pylori infection is becoming less frequent and is predominantly acquired in childhood.
A glycoprotein H (gH)-deleted herpes simplex virus type 2 (HSV-2) was evaluated as a vaccine for the prevention of HSV-induced disease. This virus, which we term a DISC (disabled infectious single cycle) virus, can only complete one replication cycle in normal cells and should thus be safe yet still able to stimulate broad humoral and cell-mediated antiviral immune responses. A gH-deleted HSV-2 virus that has been tested as a vaccine in the guinea pig model of recurrent HSV-2 infection was constructed. Animals vaccinated with DISC HSV-2 showed complete protection against primary HSV-2-induced disease, even when challenged 6 months after vaccination. In addition, the animals were almost completely protected against recurrent disease. Even at low vaccination doses, there was a high degree of protection against primary disease. A reduction in recurrent disease symptoms was also observed following therapeutic vaccination of animals already infected with wild type HSV-2.
The vaccine potential of a mutant herpes simplex virus (HSV) type 1, with a deletion in the glycoprotein H (gH) gene, was evaluated. The virus requires a gH-expressing cell line for multi-cycle growth but can complete a single cycle of infection in noncomplementing cells. Such viruses, termed DISC (disabled infectious single cycle) viruses, should be safe, yet still able to stimulate humoral and cell-mediated responses against a broad range of virus antigens in vaccinated hosts. Prophylactic vaccination of guinea pigs with DISC HSV-1, by ear scarification or direct infection of the vaginal mucosa, afforded a high degree of protection against HSV-2-induced primary genital disease and reduced significantly the frequency of subsequent disease recurrence. There was also a trend toward reduced recurrence following therapeutic vaccination of animals already infected with HSV-2. DISC HSV vaccination, therefore, offers an effective route for control of HSV disease.
Previous studies in children have shown that Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccines can reduce nasopharyngeal carriage of H. influenzae and provide herd immunity and suggest that this effect is mediated through mucosal antibodies. As this phenomenon may operate in other invasive bacterial infections which are propagated by nasopharyngeal carriage, mucosal antibody responses to meningococcal C conjugate and A/C polysaccharide vaccines were investigated. A total of 106 school children aged 11 to 17 years were randomized to receive a single dose of either conjugate or polysaccharide vaccine in an observer-blind study. Before and at 1, 6, and 12 months after immunization, samples of unstimulated saliva were collected and assayed by enzyme-linked immunosorbent assay for group C polysaccharide-specific immunoglobulin A (IgA), IgA1, IgA2 and secretory component, IgG antibodies, and total IgG and IgA. A subset of serum samples were also assayed for specific IgA and IgG antibodies. The concentrations of specific IgA and IgG in saliva were expressed both as nanograms per milliliter and as nanograms per microgram of total IgA or IgG. One month after immunization, significant increases in antibody titers (both IgA and IgG) were observed in saliva in both groups. There were significant subsequent falls in antibody titers by 6 months. Anti-meningococcal C-specific secretory component and IgA antibody titers were closely correlated (r ؍ 0.85, P < 0.001), but there was no significant correlation between salivary and serum IgA titers, suggesting that IgA antibodies are locally produced. Significant correlation was found between salivary and serum IgG titers (r ؍ 0.52, P < 0.01), suggesting that salivary IgG may be serum derived. Compared with polysaccharide vaccine, the conjugate vaccine induced significantly higher salivary IgG responses (P < 0.05), although there were no significant differences between salivary IgA responses to the two vaccines. The conjugate vaccine induced greater salivary IgG responses than a polysaccharide vaccine. Both vaccines induced significant salivary IgA antibodies. Further studies are needed to establish the functional significance of these mucosal responses.The increased incidence of septicemia and meningitis due to group C Neisseria meningitidis in recent years in the United Kingdom, particularly among older children and young adults, has created considerable public concern (30). Currently licensed polysaccharide vaccines against group C meningococcal disease do not induce immunological memory and are poorly immunogenic in children under the age of 2 years (4, 13, 21). New conjugate vaccines have been shown to induce greater immunoglobulin G (IgG) and bactericidal antibody responses (S. Choo, Q. Zhang, J. Everard, C. Goilav, E. Hatzmann, J. Zuckermann, and A. Finn, Arch. Dis. Child 80:A71, abstr. G207, 1999), to be immunogenic in infants, and to induce immunological memory (11,(22)(23)(24)34).Haemophilus influenzae type b (Hib) conjugate vaccines have been used ...
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