[Rubella immunity in Japanese women of childbearing age, 2008-2013: commercial diagnostic laboratory data analysis].

BACKGROUND: For effective non-routine vaccination in women of childbearing age as a countermeasure against congenital rubella syndrome (CRS), it is important to know the specific age group in which fewer members have rubella immunity. METHODS: We analyzed rubella hemagglutination-inhibition (HI) antibody data (about 890,000) accumulated from 2008 through 2013 at a commercial diagnostic laboratory, which originated from the serum specimens sent mainly from obstetrics & gynecology clinics and hospital departments in Japan. Changes during the above period in the pattern of the annual curve for the prevalence of rubella antibodies (HI antibody titer > or = 8) by age, were observed. RESULTS: The antibody prevalence among women in their twenties decreased gradually from 2008 to 2013. However, the prevalence at < or = 22 years of age in the 2013 specimens was found to have risen, which we believe is the effect of the five-year interim vaccination program for high-school students that began in 2008. The lowest antibody prevalence at 23 years of age in 2013 corresponded to the highest numbers of female patients at the same age in the 2013 rubella epidemic among the adult population. CONCLUSIONS: The analysis of extensive data accumulated for rubella antibodies assayed at the commercial diagnostic laboratory was useful for monitoring the susceptibility of the women to rubella infection in Japan, and that the Oct. 1987 to Mar. 1990 birth cohort (age 23 - 25 in 2013) is a high-risk group for CRS.

Measurement of cough-wind pressure: masks for mitigating an influenza pandemic.

To assess the degree to which face masks reduce the strength of cough-wind, we measured the wind pressure in front of the mouth with and without the wearing of masks. We found that any conventional masks made from paper, cotton gauze, or non-woven fabrics reduced the wind pressure to less than one-tenth that recorded when no mask was worn.

[Rubella immunity in Japanese women 20- 39-years-old, 1999-2007: commercial diagnostic laboratory data analysis].

We analyzed rubella antibody data from hemagglutination-inhibition tests on 600,000 serum specimens from Japanese women 20- 39-years-old. Specimens had been sent by gynecology clinics nationwide to a commercial diagnostic laboratory from 1999 through 2007. Antibody-positive percentages in women in their 20s to mid 30s in 1999 to 2001 were 95%, while those in women in their early 20s from 2002 to 2007 were lower at 88% among 20-year-olds in 2002 born in 1982 and 86% among those in 2007 born in 1987. These lower percentages resulted from a change in rubella vaccination policy under which junior high school girls between 1977 and 1994-those born between 1962 and 1981-underwent mandatory rubella vaccination, while mandatory vaccination was administered to younger children, instead, from 1995. Due to this policy change, girls born between 1982 and 1987 were not subjected to mandatory vaccination. We believe that women in this group have a relatively higher risk of bearing children with congenital rubella syndrome (CRS). Additional campaigns for voluntary rubella vaccination should thus be addressed to this female cohort.

[2007 measles outbreaks among Tokyo youths: analysis of data on serum IgM antibody detection at a commercial diagnostic laboratory].

We analyzed data on measles-specific serum IgM detection at a commercial diagnostic laboratory in outbreaks among youths in the greater Tokyo area in 2007. Trends in monthly numbers of IgM antibody-positive specimens from persons aged > or =15 or <15 years from January 2000 to June 2007 corresponded well to weekly numbers of adult or pediatric patients per sentinel hospital or clinic as reported by the National Epidemiological Surveillance of Infectious Diseases (NESID). In 2007, the number of IgM-positive specimens greatly increased, mainly peaking at ages 0-1 and 18-30 years. The largest number occurred at 18 years, and the number of IgM-positive specimens in the > or =15 years group was 41% larger among males than females. The proportion of IgM-positive specimens among hospitalized patients was 22% in the >15 years or = group and 11% in the < 15 years group.

[Detection of IgM antibody to Epstein-Barr virus, 1999-2006: analysis of data collected at a commercial diagnostic laboratory in Japan].

The status of infectious mononucleosis in Japanese youth has been little studied. To gain more information, we analyzed data from tests for Epstein-Barr virus-specific IgM in about 180,000 serum specimens sent to a commercial diagnostic laboratory from clinics nationwide between 1999 and 2006. The IgM antibody to the viral capsid antigen (VCA) was assayed by indirect immunofluorescence with P3HR-1 cells. In an age-distribution graph of IgM positive specimens, two peaks were found both in young children and youth. Boys outnumbered girls in the group of children aged 0 to 3, and vice versa in the group of youth aged 15 to 25. IgM-positive specimens increased from spring to autumn only in the youth group, suggesting that infectious mononucleosis in this group occurs more during this time. Infectious mononucleosis symptoms are more severe in youth, and further epidemiological studies are needed to clarify the disease status in young Japanese adults.

[IgM antibody detection in acute viral diseases, 1995-2004: analysis of data collected at a commercial diagnostic laboratory in Japan].

We analyzed data from tests for virus-specific IgM in 376,000 serum specimens sent to a commercial diagnostic laboratory from clinics nationwide between 1995 and 2004. IgM antibodies to measles, rubella, mumps, parvo B19, and varicella-zoster viruses were tested using IgM-capture ELISA kits. Among specimens, 254,000 (68%) had documentation of age, of which 56% were sera from persons<20 and 44%> or = 20 years of age. Monthly or yearly trends in IgM antibody-positive tests in<20 year-old persons were similar to those in pediatric patients per sentinel clinic reported by the National Epidemiological Surveillance of Infectious Diseases (NESID), which collects weekly numbers of patients with designated infectious diseases from 3000 pediatrics clinics nationwide. Patterns of changes in monthly IgM positive tests in both < 20 and > or = 20 y specimens were similar, indicating that infections occur simultaneously in both children and adults. Adult IgM-positive specimens came from internal medicine clinics and from dermatology clinics for measles; from dermatology and obstetrics clinics for rubella and parvo B19; from otolaryngology clinics for mumps; and from dermatology and otolaryngology clinics for varicella-zoster virus. Analysis of large numbers of IgM test results at regular intervals may contribute to understanding of the epidemiology of these viral diseases in Japan.

Masks for influenza patients: measurement of airflow from the mouth.

In case of a new influenza pandemic, provision of masks to coughing patients could be used to slow expansion of the epidemic. To quantitatively assess the efficacy of different masks, we used an ultrasonic anemometer to measure the velocity of airflow from the mouth in coughing. We found that even the cheapest paper masks reduced the air speed to less than 1/10, implicating their effectiveness in decreasing viral spread. We therefore propose that governments provide free masks to coughing patients in the general population upon the emergence of a new human influenza virus.

Three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, retain their immunogenicity and tolerogenicity in a linked peptide.

It has been demonstrated in detail that administration of a dominant T-cell determinant to animals induces activation or immunological tolerance of T cells. However, it has not been determined whether multiple T-cell determinants, when integrated into a single peptide, retain their potential to induce T-cell activation and tolerance. We prepared a synthetic peptide comprising three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, and investigated the immunogenicity and tolerogenicity of each T-cell determinant in the linked peptide by means of lymph node cell proliferation assays using mice. Lymph node cells from mice immunized with each of the three T-cell determinants proliferated against the linked peptide in a dose-dependent manner, similar to that of the immunized peptide. Lymph node cells from mice immunized with the linked peptide proliferated against all of the three T-cell determinants. In addition, the degree of proliferation against the three T-cell determinants occurred according to their original immunogenicity, as observed in the native protein antigens. Oral administration of the linked peptide to mice before they were immunized with Cry j 1 and Cry j 2 inhibited lymph node cell proliferation against the three T-cell determinants, depending on the dose of the linked peptide administered. In conclusion, it was demonstrated that three T-cell determinants retain their original immunogenicity and tolerogenicity in a linked peptide comprising them.

Analysis of the major epitope of the alpha2 chain of bovine type I collagen in children with bovine gelatin allergy.

BACKGROUND: Anaphylaxis to measles, mumps, and rubella vaccines has been reported. It has been found that most of these reactions to live vaccines are caused by type I allergy with the bovine gelatin present in the vaccines as an allergen. Gelatin mainly includes denatured type I collagen, which consists of alpha1 and alpha2 chains. We previously reported that allergic reactions to gelatin are caused by the type I collagen alpha2 (alpha2[I]) chain. OBJECTIVE: To aid in the development of gelatin that has little or no allergenicity in human subjects, we investigated epitopes of bovine alpha2(I) chain with use of IgE in gelatin-sensitive children. METHODS: Serum samples were collected from 15 patients who had systemic allergic reactions to vaccines and high levels of specific IgE to bovine gelatin. Eleven overlapping recombinant proteins that cover bovine alpha2(I) were prepared with a bacterial expression vector. We examined IgE reactivity to these recombinant proteins by means of ELISA. Fifteen peptides covering a major reactive recombinant protein were synthesized. The IgE-reacting epitope was identified by means of IgE-ELISA inhibition with these synthetic peptides and pooled serum from the patients. RESULTS: We found that of the 15 patients, 13 showed IgE reactivity to a recombinant protein (no. 3) spanning the central region of the collagenous domain ((418)Gly-(662)Pro). Furthermore, all 13 patients showed IgE reactivity to the 4-kd recombinant protein (no. 3a) spanning the region from (461)Pro to (500)Glu. In IgE-ELISA inhibition we found that a minimum IgE epitope of gelatin allergen was composed of the 10-amino-acid sequence (485)Ile-Pro-Gly-Glu-Phe-Gly-Leu-Pro-Gly-Pro(494). This sequence is not observed in the human type I collagen alpha1 and alpha2 chains, nor is it found in the bovine type I collagen alpha1 chain. CONCLUSIONS: We found that Ile-Pro-Gly-Glu-Phe-Gly-Leu-Pro-Gly-Pro is a major IgE epitope of the alpha2 chain of bovine type I collagen in patients with gelatin allergy. The degree of anaphylaxis to gelatin in vaccines might be reduced by digestion of this IgE-binding site in gelatin.

DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response.

To establish a new immunotherapy for type I allergic diseases without allergic side effects, we attempted to develop a DNA vaccine encoding both a CD4+ T cell epitope site in a major Japanese cedar pollen allergen (Cry j 2) and an invariant chain (Ii) for the delivery of the epitope peptide into the MHC class II loading pathway. We constructed a plasmid DNA encoding the Ii mutant either by replacement of the core CLIP (class II-associated invariant chain peptide) with a peptide corresponding to the major Cry j 2 CD4+ T cell epitope in BALB/c mice, designated as p247-258 (pCPCJ2), or by fusion of the Ii with p247-258 at the C terminus (pIiCJ2). As expected, repeated inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 induced no antibody response to Cry j 2. In contrast, intramuscular inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 predominantly induced p247-258-specific Th1 cells, resulting in the inhibition of IgE response to subsequent Cry j 2 injections. Our results demonstrated that the plasmid DNA encoding the CD4+ T cell epitope and Ii can induce epitope-specific CD4+ T cell responses in vivo and the potential to regulate type I allergic reaction without allergic side effects.

Isolation and characterization of cDNAs that encode homologs of a pathogenesis-related protein allergen from Cryptomeria japonica.

Many plant pathogenesis-related (PR) proteins are allergenic. We isolated three cDNAs, Cry j 3.1, Cry j 3.2, and Cry j 3.3, that encoded homologs of Jun a 3, a PR protein allergen in Juniperus ashei, from a cDNA library derived from the pollen of Cryptomeria japonica. The predicted amino acid sequences encoded by the three cDNAs were more than 85% identical to each other and about 57% identical to the sequence of Jun a 3. The Cry j 3 genes seemed to form a small multigene family in the genome of C. japonica. Expression of Cry j 3 was strong in roots and in female and male strobili; expression was weaker in cotyledons, leaves, stems, and pollen grains.