Immunogenicity of a monovalent pandemic influenza A H1N1 virus vaccine with or without prior seasonal influenza vaccine administration.

The immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We conducted a retrospective analysis of immunogenicity of 243 health care workers (number of sTIV-positive [sTIV(+)] subjects, 216; number of sTIV(-) subjects, 27) by hemagglutination inhibition. There was no significant difference in the ratios of antibody titers of ≥40 (41.2% versus 48.1%; P = 0.49) and fold increases in geometric mean titer (3.8 versus 4.5; P = 0.37). sTIV injected 7 to 10 days prior to A/H1pdm vaccine administration did not interfere with the immunogenicity of the latter.

Novel antiviral characteristics of nanosized copper(I) iodide particles showing inactivation activity against 2009 pandemic H1N1 influenza virus.

We investigated the antiviral activity of nanosized copper(I) iodide (CuI) particles having an average size of 160 nm. CuI particles showed aqueous stability and generated hydroxyl radicals, which were probably derived from monovalent copper (Cu(+)). We confirmed that CuI particles showed antiviral activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by plaque titration assay. The virus titer decreased in a dose-dependent manner upon incubation with CuI particles, with the 50% effective concentration being approximately 17 µg/ml after exposure for 60 min. SDS-PAGE analysis confirmed the inactivation of the virus due to the degradation of viral proteins such as hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR) spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution, and radical production was found to be blocked by the radical scavenger N-acetylcysteine. Taken together, these findings indicate that CuI particles exert antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful material for protecting against viral attacks and may be suitable for applications such as filters, face masks, protective clothing, and kitchen cloths.

Immunogenicity of a monovalent pandemic influenza A H1N1 vaccine in health-care workers of a university hospital in Japan.

A phase III observational study evaluating a single-dose of an inactivated, split-virus, unadjuvanted AH1pdm vaccine in HCW was conducted. A safe and effective vaccine was needed after the emergence of AH1pdm in April 2009. We analyzed the immunogenicity and safety of the vaccine. A total of 409 subjects were enrolled and given 15 µg hemagglutinin antigen by s.c. injection. Antibody titers were measured using hemagglutination-inhibition antibody assays before vaccination and 28 days after. The co-primary immunogenicity end-points were the proportion of subjects with antibody titers of 1:40 or more, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in geometric mean titer. We collected 389 pair samples. Antibody titers of 1:40 or more were observed in 148 of 389 subjects (38.0%, 95% CI: 33.2-42.9). The immunogenicity was also confirmed in other end-points, but was not sufficient and was lower than in previous reports. A total of 96 of adverse events was reported: 51 local events and 57 systemic events. There were 12 subjects with both local and systemic events. Nearly all events were mild to moderate except in four subjects. A single 15-µg dose of AH1pdm vaccine did not induce sufficient immunogenicity in HCW, with mild-to-moderate vaccine-associated adverse events. We need to consider further improvement of the AH1pdm vaccine program in HCW for the prevention of nosocomial infection, as well as for the benefit of HCW.

[Influenza telephone consultation target the general public--2003-2004, 2004-2005].

The NPO Biomedical Science Association provided telephone consultation, including contacts by fax and email, targeting the general public within the framework of influenza control measures worked out by the Japanese Ministry of Health, Labor and Welfare (MHLW). We received 2,813 inquiries during the 2003-2004 flu season and 2,444 inquiries during the 2004-2005 season. By month, the highest number was in October-November, accounting for 42.6%. The preceding season showed a similar trend. By gender, 72.5% of those seeking advice were women. By area of residence, the highest number was living in metropolitan Tokyo, and the remainder lived in the prefectures of Kanagawa, Chiba, Saitama, Nagano, Shizuoka, and Ibaraki in this order. We received no inquiries from the prefectures of Shimane or Saga. By occupation, housewives accounted for 1,114 inquiries (45.6%), followed by private companies with 447 inquiries (18.3%) and health-care providers with 227 inquiries (9.3%), similar to the 2003-2004 flu season. By subject, 1,545 inquiries concerned vaccines (62.2%) mainly, the pros and cons of vaccination, adverse reactions, and the number of inoculations required. Inquiries about pregnancy, infants and young children, and breast-feeding accounted for 19.2%. Inquiries on vaccine shortages during the 2004-2005 flu season (7), SARS (22), and bird flu (22) decreased compared to the previous season, while the number of consultations on antiviral agents increased (209). In discussing how information on influenza should be communicated to the public, we propose that "Influenza Q & A" provided by the Infectious Diseases Surveillance Center of the NIID, MHLW, should include information on influenza specifically addressing pregnant woman and breast-feeding or child-rearing mothers.

Genetic characterization of Yokose virus, a flavivirus isolated from the bat in Japan.

Yokose virus (strain Oita-36) was isolated from the bat in Japan in 1971. In the present study, we determined complete nucleotide sequences of Yokose virus using RT-PCR and RACE techniques. Yokose virus genome consists of 10,857 nucleotides in length (accession no. AB114858), containing a single open reading frame (3425 amino acids) encoding 11 viral proteins. We deduced the boundaries of each protein in the polyprotein sequence according to the protein cleavage sites of other flaviviruses. The nucleotide sequences of the 5' and 3' nontranslated region (NTR) and amino acid sequences of individual proteins of the virus were compared with those of six other flaviviruses including Japanese encephalitis virus, dengue-2 virus, yellow fever virus, West Nile virus, tick-borne encephalitis virus, and Rio Bravo virus or Modoc virus. Yokose virus demonstrated the highest similarity to yellow fever virus. Yokose virus also has CS1 motif, which are well-conserved specifically in mosquito-born flaviviruses, in its 3' NTR. When a part of the NS5 amino acid sequence (345 amino acids) was compared with those of other four flaviviruses, Entebbe bat virus, Sokuluk virus, Sepik virus, and yellow fever virus, the three former viruses are more closely related to Yokose virus than yellow fever virus. Human sera from dengue-virus-infected case and yellow fever vaccine reacted with the viral proteins. Moreover, human serum from a yellow fever vaccine weakly neutralized Yokose virus. Our results suggest that there are cross-reactive antigenicities among Yokose virus and other flaviviruses.

Antibody responses induced by immunization with a Japanese rabies vaccine determined by neutralization test and enzyme-linked immunosorbent assay.

The immunogenicity of a Japanese purified chick embryo cell culture rabies vaccine (PCECV) was examined. Serum samples were obtained from 86 subjects after pre-exposure or post-exposure prophylaxis. Rabies antibody titres were determined by neutralization test and enzyme-linked immunosorbent assay (ELISA). Titres higher than 0.5 international units (IU)/ml were demonstrated by neutralization test in all the 19 subjects after three-time pre-exposure immunization on days 0, 30 and 180. Titres higher than 0.5IU/ml were also demonstrated by neutralization test in all the 23 subjects after four-time post-exposure immunization on days 0, 3, 7 and 14. There was a correlation between neutralization and ELISA antibody titres (r=0.697); however, neutralization titers were higher than ELISA titres for most of the samples. The results suggest that current Japanese rabies vaccine induces recommended levels of neutralizing antibodies after pre- and post-exposure prophylaxes.

Development of a particle agglutination assay system for detecting Japanese encephalitis virus-specific human IgM, using hydroxyapatite-coated nylon beads.

Japanese encephalitis virus-specific IgM is a reliable indicator for serodiagnosis of Japanese encephalitis. A particle agglutination (PA) assay system was developed to detect anti-Japanese encephalitis virus IgM in human serum samples. The newly developed PA assay consisted of hydroxyapatite-coated nylon beads and V-bottom 96-well microplates. Hydroxyapatite-coated nylon beads were coated with Japanese encephalitis virus antigens. Japanese encephalitis virus antigen-coated, hydroxyapatite-coated nylon beads agglutinated in the IgM-captured wells when anti-Japanese encephalitis virus IgM-positive serum samples were used. A button pattern was formed at the bottom of the wells when anti-Japanese encephalitis virus IgM-negative serum samples were used. Thirty anti-Japanese encephalitis virus IgM-positive serum samples from Japanese encephalitis-confirmed cases were tested by the PA assay. All these serum samples were determined to be Japanese encephalitis virus IgM-positive. IgM titers determined by the PA assay corresponded to those determined by enzyme-linked immunosorbent assay. The titers were consistent in two independent PA assays. These results indicate that the newly developed PA assay is a reliable method for detecting anti-Japanese encephalitis virus IgM in human serum samples and that this assay will be a suitable diagnostic system especially in rural areas of Asia.