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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

Humoral responses.A–B: IgG serum antibodies specific to A/California/04/2009 (A) or A/PR8/34 (B) H1N1 influenza virus were determined at week 1, 3, 5 in the group of mice that were intramuscularly immunized with 10 µg of VLPs. Titers are expressed as the highest dilution of serum having a mean optical density at 450 nm greater than the mean plus 2 standard deviations above naive serum samples. Significantly higher IgG titers against A/California/04/2009 or PR8 viruses were detected at week 3 compared to week 1 (P<0.01); and at week 5 compared to week 3 (P<0.001). C–D: IgG2a and IgG1 responses. Serum was serially diluted and ELISA was performed for serum antibodies specific to A/California/04/2009 (C) or PR8 viruses (D). E–F: HAI titers. HAI titers against A/California/04/2009 (E) or A/PR8/34 (F) viruses at week 0, 1, 3 and 5 after a single immunization were determined. A/California/04/2009 infected sera at 5 weeks after infection were used as control. Significant HAI titers against A/California/04/2009 viruses were determined at week 5 compared to week 3 or week 1 (P<0.01). Significant HAI titers against A/PR8 viruses were also determined at week 5 compared to week 1 (P<0.01).
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pone-0009161-g002: Humoral responses.A–B: IgG serum antibodies specific to A/California/04/2009 (A) or A/PR8/34 (B) H1N1 influenza virus were determined at week 1, 3, 5 in the group of mice that were intramuscularly immunized with 10 µg of VLPs. Titers are expressed as the highest dilution of serum having a mean optical density at 450 nm greater than the mean plus 2 standard deviations above naive serum samples. Significantly higher IgG titers against A/California/04/2009 or PR8 viruses were detected at week 3 compared to week 1 (P<0.01); and at week 5 compared to week 3 (P<0.001). C–D: IgG2a and IgG1 responses. Serum was serially diluted and ELISA was performed for serum antibodies specific to A/California/04/2009 (C) or PR8 viruses (D). E–F: HAI titers. HAI titers against A/California/04/2009 (E) or A/PR8/34 (F) viruses at week 0, 1, 3 and 5 after a single immunization were determined. A/California/04/2009 infected sera at 5 weeks after infection were used as control. Significant HAI titers against A/California/04/2009 viruses were determined at week 5 compared to week 3 or week 1 (P<0.01). Significant HAI titers against A/PR8 viruses were also determined at week 5 compared to week 1 (P<0.01).

Mentions: To evaluate VLP immunogenicity, groups of mice (n = 12) were immunized intramuscularly with 10 µg of VLPs (approximately 1 µg HA). We determined the levels of total IgG antibody responses specific to the A/California/04/2009 and cross reactive to the antigenically different A/PR/8/1934 virus (A/PR8) (Fig. 2AB) at 1, 3, and 5 weeks after a single immunization with VLPs. IgG responses specific to the A/California/04/2009 virus and cross reactive to the PR8 virus increased with time post immunization (P<0.01), indicating the progressive maturation of virus-specific antibodies. Even with a low dose of VLP (0.1 µg), a similar pattern of antibody levels that increased up to 5 weeks after vaccination was observed (Table 1). Although the difference was 100 fold between high (10 µg) and low (0.1 µg) VLP vaccine doses, the antibody titers showed only around a 3 fold difference (Fig. 2, Table 1). As expected, mice immunized with VLPs induced significantly higher levels of IgG antibodies specific to the homologous virus by over 60 fold, compared to A/PR8 virus, which indicates that these two strains are distantly related in terms of antigenic properties.


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

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

Humoral responses.A–B: IgG serum antibodies specific to A/California/04/2009 (A) or A/PR8/34 (B) H1N1 influenza virus were determined at week 1, 3, 5 in the group of mice that were intramuscularly immunized with 10 µg of VLPs. Titers are expressed as the highest dilution of serum having a mean optical density at 450 nm greater than the mean plus 2 standard deviations above naive serum samples. Significantly higher IgG titers against A/California/04/2009 or PR8 viruses were detected at week 3 compared to week 1 (P<0.01); and at week 5 compared to week 3 (P<0.001). C–D: IgG2a and IgG1 responses. Serum was serially diluted and ELISA was performed for serum antibodies specific to A/California/04/2009 (C) or PR8 viruses (D). E–F: HAI titers. HAI titers against A/California/04/2009 (E) or A/PR8/34 (F) viruses at week 0, 1, 3 and 5 after a single immunization were determined. A/California/04/2009 infected sera at 5 weeks after infection were used as control. Significant HAI titers against A/California/04/2009 viruses were determined at week 5 compared to week 3 or week 1 (P<0.01). Significant HAI titers against A/PR8 viruses were also determined at week 5 compared to week 1 (P<0.01).
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Related In: Results  -  Collection

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pone-0009161-g002: Humoral responses.A–B: IgG serum antibodies specific to A/California/04/2009 (A) or A/PR8/34 (B) H1N1 influenza virus were determined at week 1, 3, 5 in the group of mice that were intramuscularly immunized with 10 µg of VLPs. Titers are expressed as the highest dilution of serum having a mean optical density at 450 nm greater than the mean plus 2 standard deviations above naive serum samples. Significantly higher IgG titers against A/California/04/2009 or PR8 viruses were detected at week 3 compared to week 1 (P<0.01); and at week 5 compared to week 3 (P<0.001). C–D: IgG2a and IgG1 responses. Serum was serially diluted and ELISA was performed for serum antibodies specific to A/California/04/2009 (C) or PR8 viruses (D). E–F: HAI titers. HAI titers against A/California/04/2009 (E) or A/PR8/34 (F) viruses at week 0, 1, 3 and 5 after a single immunization were determined. A/California/04/2009 infected sera at 5 weeks after infection were used as control. Significant HAI titers against A/California/04/2009 viruses were determined at week 5 compared to week 3 or week 1 (P<0.01). Significant HAI titers against A/PR8 viruses were also determined at week 5 compared to week 1 (P<0.01).
Mentions: To evaluate VLP immunogenicity, groups of mice (n = 12) were immunized intramuscularly with 10 µg of VLPs (approximately 1 µg HA). We determined the levels of total IgG antibody responses specific to the A/California/04/2009 and cross reactive to the antigenically different A/PR/8/1934 virus (A/PR8) (Fig. 2AB) at 1, 3, and 5 weeks after a single immunization with VLPs. IgG responses specific to the A/California/04/2009 virus and cross reactive to the PR8 virus increased with time post immunization (P<0.01), indicating the progressive maturation of virus-specific antibodies. Even with a low dose of VLP (0.1 µg), a similar pattern of antibody levels that increased up to 5 weeks after vaccination was observed (Table 1). Although the difference was 100 fold between high (10 µg) and low (0.1 µg) VLP vaccine doses, the antibody titers showed only around a 3 fold difference (Fig. 2, Table 1). As expected, mice immunized with VLPs induced significantly higher levels of IgG antibodies specific to the homologous virus by over 60 fold, compared to A/PR8 virus, which indicates that these two strains are distantly related in terms of antigenic properties.

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