flu
Influenza vaccine powder formulation development: spray-freeze-drying and stability evaluation.

Maa YF, Ameri M, Shu C, Payne LG, Chen D.

PowderJect Vaccines, Incorporated, 8551 Research Way Boulevard, Middleton, Wisconsin 53562, USA. ymaa alzus.jnj.com

The purpose of this study was to develop a spray-freeze-drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry-powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high-density particles-a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long-term physical and biochemical stability. One formulation, in particular, containing sub-unit vaccine (45 microg of antigen in 1 mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912-1923, 2004

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15176078&dopt=Abstract flu, flu medicine, tamiflu



flu
Utility of reverse transcriptase PCR for rapid diagnosis of influenza a virus infection and detection of amantadine-resistant influenza a virus isolates.

Pachucki CT, Khurshid MA, Nawrocki J.

Department of Infectious Disease and Department of Laboratory Medicine and Pathology, Edward Hines Jr. Veterans Administration Hospital, 111-P, Hines, IL 60141, USA. constance.pachucki med.va.gov

A reverse transcriptase PCR was developed to detect 50 or 5,000 RNA copies of influenza A virus per ml in throat swab specimens. The assay was more sensitive than the Directigen Flu A test. The technique was also used to detect amantadine-resistant isolates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15184474&dopt=Abstract flu, flu medicine, tamiflu



flu
Social representation of a food risk: the Hong Kong avian bird flu epidemic.

Joffe H, Lee NY.

Department of Psychology, University College London, UK. h.joffe ucl.ac.uk

The paper explores the social representation of the 2001 Hong Kong avian bird flu epidemic from the perspective of local women. Fifty women were asked to describe their first thoughts about the flu, and these were subsequently explored. Thematic analysis of the semi-structured interviews revealed that the first thoughts were characterized by: (a) the origin of the epidemic, (b) anchors for it, (c) emotions about it, and (d) images of it. Aspersion concerning the lack of hygiene of Mainland Chinese chicken rearers and chicken sellers in Hong Kong dominated the interviews. Other environmental factors were also stressed, as was regulation leniency and a drive to profit. Comparisons between old traditions and newer practices formed a central feature. The findings are discussed in terms of their continuity with western risk findings as well as their specific cultural nuances.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15231054&dopt=Abstract flu, flu medicine, tamiflu



flu
Influenza vaccination by race among disabled community dwelling older women.

Frick KD, Scanlon DP, Bandeen-Roche K, Kasper JD, Simonsick EM, Sullivan EM.

Johns Hopkins Bloomberg School of Public Health, Department of Health Policy and Management, USA.

Disabled older adults have been shown to be at risk for underutilization of some preventive services relative to able-bodied individuals. The Women's Health and Aging Study surveyed female Medicare enrollees in Baltimore, Maryland, who were among the most disabled community-dwelling women at the start of the study. Longitudinal survey data from the study were used to test for the existence or emergence of racial variation in influenza vaccination rates, for which racial variation has been shown in the general population. The primary analysis, using data on the same women before and after Medicare flu shot coverage began, suggested that influenza vaccination rates increased after Medicare coverage began and that there was no difference by race. A secondary analysis using data on women who were interviewed only after Medicare flu shot coverage began showed some racial variation, although the difference may have been larger prior to coverage. The utilization rate did not approach the Healthy People 2010 target.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15253375&dopt=Abstract flu, flu medicine, tamiflu



flu
Anticancer and antiviral activities of Youngia japonica (L.) DC (Asteraceae, Compositae).

Ooi LS, Wang H, Luk CW, Ooi VE.

Department of Biology, The Chinese University of Hong Kong, Shatin, NT.

Aqueous and ethanol extracts of Youngia japonica (also known as Oriental hawksbeard) were tested in vitro for anti-tumor activity against three cell lines, human promyelocytic leukaemia (HL-60), human myelogenous leukaemia (chronic K-562) and mouse Sarcoma 180 (S-180), and for antiviral activity against respiratory syncytial virus (RSV), influenza A virus (Flu A) and herpes simplex virus type 1 (HSV-1) by cytopathic effect (CPE) reduction assay. Hot water extract of Youngia japonica inhibited cell proliferation and growth of all cancer cell lines to various extent. K-562 cells were the most sensitive to the extract whereas S-180 cells were the least. It did not show any significant cytotoxic effects on normal mammalian Vero cells up to the concentration of 450 microg/mL. The ethanol extract of whole plant of Youngia japonica exhibited antiviral activity against RSV cultured in HEp-2 cells, but did not have any activity against Flu A and HSV-1. Two partially purified fractions (Fr.10 and Fr.11) from the 95% ethanol extract exhibited significant anti-RSV with 50% inhibitory concentration (IC50) in the range of 3.0-6.0 microg/mL. The ratio of the viral titer reduction in the absence (viral control) and presence of the maximal non-cytotoxic concentration (MNCC) of the Fr.10 and Fr.11 was both estimated to be 1 x 10(4) (RF, viral titer reduction factors), indicating that their anti-RSV activity was high enough to justify for further analysis. Our preliminary analysis showed that the antiviral ingredients were likely to contain phenolic compounds including tannins by chemical tests.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15261971&dopt=Abstract flu, flu medicine, tamiflu



flu
Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys.

Fan J, Liang X, Horton MS, Perry HC, Citron MP, Heidecker GJ, Fu TM, Joyce J, Przysiecki CT, Keller PM, Garsky VM, Ionescu R, Rippeon Y, Shi L, Chastain MA, Condra JH, Davies ME, Liao J, Emini EA, Shiver JW.

Department of Vaccine and Biologics Research, Merck Research Laboratories, 770 Sumneytown Pike, P.O. Box 4, WP16-306, West Point, PA 19486, USA.

A universal influenza virus vaccine that does not require frequent updates and/or annual immunizations will offer significant advantages over current seasonal flu vaccines. The highly conserved influenza virus A M2 membrane protein has been previously suggested as a potential antigen target for such a vaccine. Here, we report systematic evaluation of M2 peptide conjugate vaccines (synthetic peptides of M2 extracellular domain conjugated to keyhole limpet hemocyanin (KLH) or Neisseria meningitidis outer membrane protein complex (OMPC)) in mice, ferrets, and rhesus monkeys. The conjugate vaccines were highly immunogenic in all species tested and were able to confer both protection against lethal challenge of either H1N1 or H3N1 virus in mice and reduce viral shedding in the lower respiratory tracts of mice and ferrets. The protection against lethal challenge in mice could also be achieved by passive transfer of monkey sera containing high M2 antibody titers. In addition, we showed that M2 antisera were cross reactive with M2 peptides derived from a wide range of human influenza A strains, but they failed to react with M2 peptides of the pathogenic H5N1 virus (A/Hong Kong/97). The data presented here will permit better understanding of the potential of an M2-based vaccine approach.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15297047&dopt=Abstract flu, flu medicine, tamiflu