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Virus-like particle vaccine protects against 2009 H1N1 pandemic influenza virus in mice.

Quan FS, Vunnava A, Compans RW, Kang SM - PLoS ONE (2010)

Bottom Line: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines.VLP immune sera also showed HAI responses against diverse geographic pandemic isolates.The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.

ABSTRACT

Background: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines.

Methodology/principal findings: We generated influenza virus-like particles (VLPs) containing proteins derived from the A/California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection.

Conclusion/significance: This study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production.

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Related in: MedlinePlus

Protection of mice from lethal influenza virus challenge.A–B: Protection against A/California/04/2009 virus challenge. Mice intramuscularly immunized with a single dose of VLPs (10 µg) were challenged with a lethal dose (100 LD50) of A/California/04/2009 virus at week 6 post immunization. Mice (n = 12) were monitored daily for 14 days for body weight changes (A) and survival rates (B). C–D: Protection against the antigenically distant A/PR8/1934 virus (10 LD50). Body weight changes (C) and survival rates (D) are shown.
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pone-0009161-g003: Protection of mice from lethal influenza virus challenge.A–B: Protection against A/California/04/2009 virus challenge. Mice intramuscularly immunized with a single dose of VLPs (10 µg) were challenged with a lethal dose (100 LD50) of A/California/04/2009 virus at week 6 post immunization. Mice (n = 12) were monitored daily for 14 days for body weight changes (A) and survival rates (B). C–D: Protection against the antigenically distant A/PR8/1934 virus (10 LD50). Body weight changes (C) and survival rates (D) are shown.

Mentions: To determine the potency of protective efficacies, mice were challenged with a high lethal dose of A/California/2009 virus (100 LD50) at 6 weeks after a single immunization with VLPs. As shown in Fig. 3, all naïve mice died after infection with the wild type A/California/2009 virus. In contrast, vaccinated mice were completely protected when challenged with the homologous A/California/2009 virus and did not show any loss in body weight (Fig. 3AB). A similar protective efficacy was observed 4 months after VLP vaccination (data not shown). To determine the potential cross protection against an antigenically distant strain, immunized mice were also challenged with A/PR8 virus (10 LD50). VLP immunized mice showed a significant level of protection, with 75% survival rates against A/PR8 virus, although the surviving mice exhibited approximately 20% transient loss in body weight (Fig. 3CD).


Virus-like particle vaccine protects against 2009 H1N1 pandemic influenza virus in mice.

Quan FS, Vunnava A, Compans RW, Kang SM - PLoS ONE (2010)

Protection of mice from lethal influenza virus challenge.A–B: Protection against A/California/04/2009 virus challenge. Mice intramuscularly immunized with a single dose of VLPs (10 µg) were challenged with a lethal dose (100 LD50) of A/California/04/2009 virus at week 6 post immunization. Mice (n = 12) were monitored daily for 14 days for body weight changes (A) and survival rates (B). C–D: Protection against the antigenically distant A/PR8/1934 virus (10 LD50). Body weight changes (C) and survival rates (D) are shown.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2820088&req=5

pone-0009161-g003: Protection of mice from lethal influenza virus challenge.A–B: Protection against A/California/04/2009 virus challenge. Mice intramuscularly immunized with a single dose of VLPs (10 µg) were challenged with a lethal dose (100 LD50) of A/California/04/2009 virus at week 6 post immunization. Mice (n = 12) were monitored daily for 14 days for body weight changes (A) and survival rates (B). C–D: Protection against the antigenically distant A/PR8/1934 virus (10 LD50). Body weight changes (C) and survival rates (D) are shown.
Mentions: To determine the potency of protective efficacies, mice were challenged with a high lethal dose of A/California/2009 virus (100 LD50) at 6 weeks after a single immunization with VLPs. As shown in Fig. 3, all naïve mice died after infection with the wild type A/California/2009 virus. In contrast, vaccinated mice were completely protected when challenged with the homologous A/California/2009 virus and did not show any loss in body weight (Fig. 3AB). A similar protective efficacy was observed 4 months after VLP vaccination (data not shown). To determine the potential cross protection against an antigenically distant strain, immunized mice were also challenged with A/PR8 virus (10 LD50). VLP immunized mice showed a significant level of protection, with 75% survival rates against A/PR8 virus, although the surviving mice exhibited approximately 20% transient loss in body weight (Fig. 3CD).

Bottom Line: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines.VLP immune sera also showed HAI responses against diverse geographic pandemic isolates.The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.

ABSTRACT

Background: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines.

Methodology/principal findings: We generated influenza virus-like particles (VLPs) containing proteins derived from the A/California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection.

Conclusion/significance: This study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production.

Show MeSH
Related in: MedlinePlus