Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin

• Published in: Vaccine Vol. 25; no. 19; pp. 3871 - 3878
• Main Authors: Bright, Rick A, Carter, Donald M, Daniluk, Shannon, Toapanta, Franklin R, Ahmad, Attiya, Gavrilov, Victor, Massare, Mike, Pushko, Peter, Mytle, Nutan, Rowe, Thomas, Smith, Gale, Ross, Ted M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 10.05.2007; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibodies, Viral - blood; Applied microbiology; Baculoviridae; Baculovirus; Biological and medical sciences; Cells, Cultured; Disease control; Female; Ferrets; Fundamental and applied biological sciences. Psychology; Hemagglutination Inhibition Tests; Hemagglutination-inhibition; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Immune response; Infections; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza virus; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mustela; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Protein expression; Proteins; R&D; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Research & development; Spodoptera; Spodoptera frugiperda; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; Viral infections; Virion - immunology; Virology; Virus-like particle; Viruses; VLP; Virus-like particle; VLP; Hemagglutination-inhibition; Influenza; Immune response; Hemagglutinin; Recombinant virus; Virus like particle; Orthomyxoviridae; Influenzavirus; Infection; Virus; Hemagglutination; Viral disease; Flulike syndrome
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.01.106

Abstract Influenza virus is a highly infectious respiratory pathogen that results in severe morbidity and mortality. The current licensed trivalent vaccine formulations in the U.S. are made from virus grown in allantoic fluid from infected hen eggs that is then chemically inactivated and split into subunit components. These vaccines elicit antibodies, primarily to the viral hemagglutinin (HA), which are efficacious in healthy adults, but are limited in protecting high risk individuals, such as the elderly and immunocompromised. To address the need for improved influenza vaccines and the limitations of egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine against influenza infection. VLPs, based on the A/Fujian/411/2002 (H3N2) isolate, were purified from the supernatants of Spodoptera frugiperda Sf9 insect cells following infection of baculovirus vectors encoding an expression cassette comprised of only three influenza virus structural proteins, hemagglutinin (HA), neuraminidase (NA), and matrix (M1). Mice or ferrets were vaccinated intramuscularly with VLPs in a dose sparing experiment, based on HA concentration (3 μg–24 ng), and the immune responses were compared to responses elicited in animals vaccinated with recombinant HA (rHA) or inactivated whole influenza virions (WIV). All vaccinated animals had high titer anti-HA antibodies regardless of the vaccine immunogen and animals vaccinated with the highest doses of VLPs (3 μg and 600 ng) also had antibodies against NA. Purified rHA elicited primarily IgG1 antibodies, which is indicative of a T helper (Th) type 2 response, whereas mice vaccinated with the VLPs or WIV were associated with a dominant Th1 immune response (IgG2a and IgG2b). Interestingly, VLPs elicited antibodies that recognized a broader panel of antigenically distinct H3N2 viral isolates compared to rHA or WIV in a hemagglutination-inhibition (HAI) assay.