title: Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment.
abstract: There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.
authors.affiliation: Washington University School of Medicine, Department of Radiology, St. Louis, Missouri 63110, United States.
authors.forename: Shaw-Wei David
authors.initials: SW
authors.lastname: Tsen
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United States.
authors.forename: Nisha
authors.initials: N
authors.lastname: Donthi
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: La
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United States.
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Hsieh
authors.affiliation: National Taiwan University, College of Medicine, Taipei 10617, Taiwan.
authors.forename: Yen-Der
authors.initials: YD
authors.lastname: Li
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United States.
authors.forename: Jayne
authors.initials: J
authors.lastname: Knoff
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Chen
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United StatesdJohns Hopkins Medical Institutions, Department of Obstetrics and Gynecology, Baltimore, Maryland 21231, United StateseJohns Hopkins Medical Institutions.
authors.forename: Tzyy-Choou
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, Maryland 21231, United StatesfJohns Hopkins Medical Institutions, Department of Oncology, Baltimore, Maryland 21231, United States.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Washington University School of Medicine, Department of Radiology, St. Louis, Missouri 63110, United StatesgWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, St. Louis, Missouri 63110, United StateshWashington.
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.affiliation: Arizona State University, Department of Physics and Center for Biophysics, Tempe, Arizona 85287, United States.
authors.forename: Kong-Thon
authors.initials: KT
authors.lastname: Tsen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002460:Cell Line; D004285:Dogs; D005260:Female; D006386:Hemagglutination Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000737:chemistry*; D007251:Influenza, Human / Q000517:prevention & control; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000737:chemistry
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated