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Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin.
Vaccine. 2007 May 10; 25(19):3871-8.V

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 microg-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 microg 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.

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Authors+Show Affiliations

Bright RA
Novavax, Inc., Rockville, MD 20850, USA. rbright@novavax.com
Carter DM
No affiliation info available
Daniluk S
No affiliation info available
Toapanta FR
No affiliation info available
Ahmad A
No affiliation info available
Gavrilov V
No affiliation info available
Massare M
No affiliation info available
Pushko P
No affiliation info available
Mytle N
No affiliation info available
Rowe T
No affiliation info available
Smith G
No affiliation info available
Ross TM
No affiliation info available

MeSH

AnimalsAntibodies, ViralBaculoviridaeCells, CulturedFemaleFerretsHemagglutination Inhibition TestsHemagglutinin Glycoproteins, Influenza VirusInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza VaccinesMiceMice, Inbred BALB COrthomyxoviridae InfectionsRecombinant ProteinsSpodopteraVaccinationVaccines, InactivatedVirion

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17337102

Citation

Bright, Rick A., et al. "Influenza Virus-like Particles Elicit Broader Immune Responses Than Whole Virion Inactivated Influenza Virus or Recombinant Hemagglutinin." Vaccine, vol. 25, no. 19, 2007, pp. 3871-8.
Bright RA, Carter DM, Daniluk S, et al. Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. Vaccine. 2007;25(19):3871-8.
Bright, R. A., Carter, D. M., Daniluk, S., Toapanta, F. R., Ahmad, A., Gavrilov, V., Massare, M., Pushko, P., Mytle, N., Rowe, T., Smith, G., & Ross, T. M. (2007). Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. Vaccine, 25(19), 3871-8.
Bright RA, et al. Influenza Virus-like Particles Elicit Broader Immune Responses Than Whole Virion Inactivated Influenza Virus or Recombinant Hemagglutinin. Vaccine. 2007 May 10;25(19):3871-8. PubMed PMID: 17337102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. AU - Bright,Rick A, AU - Carter,Donald M, AU - Daniluk,Shannon, AU - Toapanta,Franklin R, AU - Ahmad,Attiya, AU - Gavrilov,Victor, AU - Massare,Mike, AU - Pushko,Peter, AU - Mytle,Nutan, AU - Rowe,Thomas, AU - Smith,Gale, AU - Ross,Ted M, Y1 - 2007/02/15/ PY - 2006/11/07/received PY - 2007/01/15/revised PY - 2007/01/23/accepted PY - 2007/3/6/pubmed PY - 2007/6/30/medline PY - 2007/3/6/entrez SP - 3871 EP - 8 JF - Vaccine JO - Vaccine VL - 25 IS - 19 N2 - 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 microg-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 microg 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. SN - 0264-410X UR - https://www.unboundmedicine.com/medline/citation/17337102/Influenza_virus_like_particles_elicit_broader_immune_responses_than_whole_virion_inactivated_influenza_virus_or_recombinant_hemagglutinin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(07)00135-1 DB - PRIME DP - Unbound Medicine ER -