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B L Innis

Publications and source records attributed to B L Innis.

80 records · Page 5Linked to original sources

Identification of continuous epitopes of the envelope glycoprotein of dengue type 2 virus.

We reacted 490 hexapeptides homologous to the amino acid sequence of the dengue 2 (DEN-2) virus envelope glycoprotein with antisera from 7 patients with primary DEN-2 virus infections to identify the continuous epitopes recognized by human IgG. There were 124 peptides in 25 clusters (domains) that bound 2 or more antisera. Twenty-two peptides in 7 domains bound all 7 convalescent DEN-2 virus antisera tested, and thus appeared to represent immunodominant epitopes. The evidence that these domains represents continuous epitopes of the envelope glycoprotein is that peptide representing each domain bound multiple sera, peptide reactivity was highly ordered along the amino acid sequence, and in almost all cases, domains were regions of predicted hydrophilicity. Heterologous flavivirus antisera also exhibited binding to the majority of peptides reactive with anti-DEN-2 virus sera, though 4 candidate DEN-2 specific epitopes were identified along with an immunodominant epitope common to dengue, Japanese encephalitis and West Nile viruses. Synthetic peptides representing these epitopes may prove to be useful for a variety of purposes.

Amino Acids↗

Protection against Japanese encephalitis by inactivated vaccines.

Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.

Adolescent↗

Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy.

High cost and limited availability of the current hepatitis B virus vaccine lead to underutilization. To address this problem, we performed a vaccine trial comparing the currently recommended regimen of 20 micrograms of hepatitis B surface antigen (HBsAg) intramuscularly on days 0, 30, and 180, with a more economical regimen of 2 micrograms of HBsAg intradermally on days 0, 30, and 180. This trial was performed in 50 seronegative health care workers to assess the immunogenicity and local reactogenicity of both vaccine regimens. We found no significant difference in seroconversion between the intradermal group (96%) and the intramuscular group (100%). Mean ratios of test sample value to mean negative control value for antibody to HBsAg at 360 days were not significantly different (intradermal group, 84 +/- 26; intramuscular group, 120 +/- 22). Reactions in both groups were minor. Although the optimal dose of HBsAg was not investigated, our data demonstrate that 0.1 mL of inactivated hepatitis B virus vaccine (Heptavax-B) intradermally is immunogenic in healthy adults. Vaccination by this regimen can broaden hepatitis B virus disease prevention.

Adult↗

Molecular characterization of a hepatitis E virus isolate from Namibia.

Hepatitis E virus (HEV) causes sporadic and epidemic acute viral hepatitis in many developing countries. In Africa, hepatitis E has been documented by virus detection (reverse transcriptase polymerase chain reaction, RT-PCR) in Egypt, Chad, Algeria, Morocco and Tunisia. Cases of presumptive hepatitis E also have been documented by detection of antibody to HEV in the Sudan, Kenya, Ethiopia, Somalia, Djibouti and South Africa. Recently, we reported the recovery of 9 isolates of HEV from feces collected during an outbreak of jaundice in Namibia. These specimens were stored frozen for many years at the South African Institute for Medical Research awaiting new methods to determine the etiology of jaundice. HEV genomic sequences were detected by antigen-capture RT-PCR with primers that amplified 2 independent regions of the HEV genome (ORF-2 and ORF-3). To further characterize the HEV 83-Namibia isolates, we determined the nucleotide (nt) sequence of the 3' end of the capsid gene (296 of 1, 980 nt in ORF-2) and ORF-3 for 1 isolate. The capsid gene sequence shared 86% identity with the prototype Burma strain and up to 96% identity with other African strains at the (nt) level, and 99% identity with Burma or other Africa strains at the amino acid level. A 188 (nt) fragment amplified from ORF-3 was also highly homologous to other HEV but was too short for meaningful comparison. Phylogenetic analysis indicated that HEV 83-Namibia is closely related to other African isolates, and differs from Burmese, Mexican and Chinese HEV. These data link the HEV causing the 1983 Namibia outbreak to more recent HEV transmission in northern and sub-Saharan Africa, suggesting this subgenotype of HEV is firmly established throughout the continent.

Capsid↗

Hepatitis E virus DNA vaccine elicits immunologic memory in mice.

Injection of an expression vector pJHEV containing hepatitis E virus (HEV) structural protein open reading frame 2 gene generates a strong antibody response in BALB/c mice that can bind to and agglutinate HEV. In this study, we tested for immunologic memory in immunized mice whose current levels of IgG to HEV were low or undetectable despite 3 doses of HEV DNA vaccine 18 months earlier. Mice previously vaccinated with vector alone were controls. All mice were administered a dose of HEV DNA vaccine to simulate an infectious challenge with HEV. The endpoint was IgG to HEV determined by ELISA. Ten days after the vaccine dose, 5 of 9 mice previously immunized with HEV DNA vaccine had a slight increase in IgG to HEV. By 40 days after the vaccine dose, the level of IgG to HEV had increased dramatically in all 9 mice (108-fold increase in geometric mean titer). In contrast, no control mice became seropositive. These results indicate that mice vaccinated with 3 doses of HEV DNA vaccine retain immunologic memory. In response to a small antigenic challenge delivered as DNA, possibly less than delivered by a human infective dose of virus, mice with memory were able to generate high levels of antibody in less time than the usual incubation period of hepatitis E. We speculate that this type of response could protect a human from overt disease.

Animals↗

Distribution of dengue and Japanese encephalitis among children in rural and suburban Thai villages.

In the rainy season of 1989, IgG and IgM antibodies against dengue and Japanese encephalitis viruses (measured by enzyme-linked immunoassay [ELISA]) in serum from all primary-school children in two areas of central Thailand were sampled in order to choose a study site for more detailed epidemiological and entomological analysis. Students in three schools in the largely non-agricultural, suburban community of Bang Bua Thong, Nontaburi Province were sampled in late June and July. Of 1,477 children, 33/1,000 had recent dengue infection and 7/1,000 had recent JE infection. The rate of dengue infection in each village influenced the rate in schools, in that the rate of the school could be predicted from the proportion of students coming from each village. This result suggested that most transmission occurred in the residential environment; otherwise, the rate in each village going to a single school would be identical. Serum samples were taken in late August in the agricultural community of Hua Samrong, Chachoengsao Province. Of 748 students in two schools, 95/1,000 had signs of recent dengue infection and 32/1,000 had signs of recent JE infection. Two of 12 villages had significantly less flavivirus infection than some other villages and three villages had significantly more flavivirus infection. The children from one village had a dengue infection rate of 256 per 1,000, which was higher than the national average for the worst year (1987) previously recorded in Thailand. Within Hua Samrong, there was evidence for significant dengue transmission in one of the schools and concentrated transmission in small areas of two of the villages. The younger age group (3-8 years old) had significantly higher risk of infection by either flavivirus than older children. Elevated homes with wooden floors had significantly higher risk of dengue in the largest village. The observations from 1989 describe the epidemiological situation in rapidly developing, rural villages. This stage of development is probably being repeated throughout Southeast Asia as formerly isolated, rural villages become connected by transportation and economy to urban centers. What appears to be a single dengue outbreak based on passive surveillance conducted on a regional basis may actually be a variety of epidemiological situations. The practical implication of this conclusion is that application of a combination of vaccination and vector control should be targeted to higher risk areas in order to increase the likelihood of regional dengue virus eradication.

Adolescent↗