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. 2011 Jan;5(1):13-23.
doi: 10.1111/j.1750-2659.2010.00177.x. Epub 2010 Nov 3.

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Karoline Bragstad  1 , Cyril J Martel, Joakim S Thomsen, Kim L Jensen, Lars P Nielsen, Bent Aasted, Anders Fomsgaard
Affiliations

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Karoline Bragstad et al. Influenza Other Respir Viruses. 2011 Jan.

Abstract

Background: Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations.

Objective: In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge.

Methods: Ferrets were immunised by particle-mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses.

Results: We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross-reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross-reactive immune responses against a recent 2005 H3N2 virus challenge.

Conclusions: DNA vaccines based on pandemic or recent seasonal influenza genes induced cross-reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross-protective immunity against both contemporary and long-time drifted viruses.

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Figures

Figure 1
Figure 1
H1N1 1918 DNA vaccines induce cross‐protective immunity against a 1947 H1N1 influenza virus challenge. 1947 H1N1 virus load in nasal washings (A) was measured by real‐time RT‐PCR on the M gene and expressed as individual log‐virus copy number. Data is presented as individual log‐virus titre with linear regression lines for each vaccination group; H/N 1918 H1N1 DNA (red), H/N/NP/M 1918 H1N1 DNA (green) and control group, empty plasmid (black). A slope significantly none‐zero is indicated with an asterisk. A/New Caledonia/20/99(H1N1)‐specific serum IgG antibodies were measured by ELISA (B) and presented as mean end‐point titre with standard deviation for each vaccination group; H/N 1918 H1N1 DNA (white), H/N/NP/M 1918 H1N1 DNA (grey) and control group, empty plasmid (dotted). An asterisk indicates DNA‐vaccinated groups significantly (P < 0·05) different from the control group, empty plasmid. Haemagglutination inhibition (HI) antibodies against the 1947 H1N1 virus (C) were measured by a HI assay with 0·75% guinea pig red blood cells. Haemagglutination inhibition titres are given as geometric mean titre with 95% confidence interval. H/N 1918 H1N1 DNA (white), H/N/NP/M 1918 H1N1 DNA (grey) and control group, empty plasmid (dotted). An asterisk indicates DNA‐vaccinated groups significantly (P < 0·05) different from the control group.
Figure 2
Figure 2
1918 H1N1 DNA vaccines induce cross‐reactive immunity against a contemporary 1999 H1N1 influenza virus challenge. 1999 H1N1 virus load in nasal washings (A) was measured by real‐time RT‐PCR on the M gene and expressed as individual log‐virus copy number. Data is presented as individual log‐virus titre with linear regression lines for each vaccination group; H/N 1918 H1N1 DNA (red), H/N 1999 H1N1 DNA (green), NP/M 1918 H1N1 DNA (black) and the control groups, conventional trivalent protein vaccine (blue) and empty plasmid (orange). A slope significantly none‐zero is indicated with an asterisk. Anti‐A/New Caledonia/20/99(H1N1)‐specific IgG antibodies were measured by ELISA (B) and presented as geometric mean end‐point titres with 95% confidence interval. Vaccine groups: H/N 1918 H1N1 DNA (white), H/N 1999 H1N1 DNA (grey), NP/M 1918 DNA (black), conventional trivalent protein vaccine (striped) and empty plasmid (dotted). Day 38 pre‐challenge (day 0) was the day of the first vaccine dose. Anti‐A/New Caledonia/20/99(H1N1)‐specific IgG antibodies induced by the H/N‐1918 DNA‐vaccinated ferrets (white) compared to naïve ferrets (dotted) are presented as geometric mean end‐point titre with 95% confidence interval (C). Haemagglutination inhibition (HI) antibodies against eight haemagglutination units of A/New Caledonia/20/99(H1N1) virus (D) were measured by HI assays with 0·75% guinea pig red blood cells. Haemagglutination inhibition titres are given as geometric mean titre with 95% confidence interval. Day 38 pre‐challenge (day 0) was the day of the first vaccine dose. Pools of sera from each group were tested in duplicates against 1918 H1N1‐like swine 1931 virus (E). An asterisk indicates vaccine groups significantly (P < 0·05) different from the empty plasmid control group.
Figure 3
Figure 3
1968 H3N2 DNA vaccine induces cross‐reactivity against a contemporary 2005 H3N2 influenza virus infection. 2005 H3N2 virus load in nasal washings (A) was measured by real‐time RT‐PCR on the M gene and expressed as individual log‐virus copy number. Data is presented as individual log‐virus titre with linear regression lines for each vaccination group; H/N 1968 H3N2 DNA (red), H/N 2005 H3N2 DNA (green), conventional trivalent protein vaccine (blue) and the naïve, unvaccinated control group (black). Significant reduction (P < 0·05) in median virus titre from day 4 to 7 in the H/N 2005 DNA‐vaccinated group is indicated with an asterisk. Anti‐A/Wisconsin/67/05(H3N2)‐specific IgG serum antibodies were measured by ELISA (B) and presented as the reciprocal geometric mean titre with 95% confidence interval of the dilution correlating with an OD of one read from a standard curve included on each plate. An asterisk indicates vaccine groups significantly (P < 0·05) different from the naïve control group. Haemagglutination inhibition (HI) antibodies were measured against eight haemagglutination units of A/Aichi/2/68(H3N2) virus (C) or A/Wisconsin/67/05(H3N2) virus (D) with 0·75% guinea pig red blood cells. Haemagglutination inhibition titres are given as geometric mean titre with 95% confidence interval of the reciprocal value of the last dilution of sera completely inhibiting haemagglutination. The vaccine groups were as follows: H/N 1968 H3N2 DNA (white), H/N 2005 H3N2 DNA (grey), conventional trivalent protein vaccine (striped) and naïve unvaccinated ferrets (dotted). An asterisk indicates vaccine groups significantly (P < 0·05) different from the naïve control group.
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References

    1. Demicheli V, Jefferson T, Rivetti D, Deeks J. Prevention and early treatment of influenza in healthy adults. Vaccine 2000; 18(11–12):957–1030. - PubMed
    1. Jefferson TO, Rivetti D, Di Pietrantonj C, Rivetti A, Demicheli V. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2007. Apr 18; (2):CD001269. - PubMed
    1. Ulmer JB, Wahren B, Liu MA. Gene‐based vaccines: recent technical and clinical advances. Trends Mol Med 2006; 12(5):216–222. - PubMed
    1. Liu MA, Wahren B, Karlsson Hedestam GB. DNA vaccines: recent developments and future possibilities. Hum Gene Ther 2006; 17(11):1051–1061. - PubMed
    1. Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat Rev Genet 2008; 9(10):776–788. - PMC - PubMed

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