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1.
Figure 1

Figure 1. From: Long Term Persistence of IgE Anti-Influenza Virus Antibodies in Pediatric and Adult Serum Post Vaccination with Influenza Virus Vaccine.

Immunoblot analysis of IgE anti-influenza virus antibodies. Serum from subjects with past history of influenza virus vaccination or no infection was incubated with nitrocellulose strips containing influenza virus vaccine antigen (see Materials and Methods). Lane 1: representative blot of subject vaccinated with influenza virus vaccine, who had elevated serum IgE levels (>100 IU/ml). Lane 2: representative blot of subject vaccinated with influenza virus vaccine who had low serum IgE levels (<100 IU/ml). Lane 3: control subject, no history of infection or vaccination.

Tamar A. Smith-Norowitz, et al. Int J Med Sci. 2011;8(3):239-244.
2.
Fig 1-5

Fig 1-5. From: Serum Proinflammatory Cytokine Responses to Influenza Virus Vaccine among Women during Pregnancy versus Non-Pregnancy.

Serum proinflammatory cytokine responses to trivalent influenza virus vaccine (TIV)

Lisa M. Christian, et al. Am J Reprod Immunol. ;70(1):10.1111/aji.12117.
3.
Figure 5

Figure 5. From: Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity.

Effect of trehalose concentration on vaccine coating. (A) Effect of trehalose concentration in coating solution on () mass (per 5 microneedles) and () HA activity of coated inactivated influenza virus after reconstitution (n=4). (B) Effect of trehalose concentration in coating solution on the size of coated inactivated influenza virus particles after reconstitution (n=4).

Yeu-Chun Kim, et al. J Control Release. ;142(2):187-195.
4.
FIG. 3.

FIG. 3. From: Immunostimulant Patch Enhances Immune Responses to Influenza Virus Vaccine in Aged Mice.

LT-IS patch enhances secondary responses to influenza virus vaccine delivered by i.d. injection. Young (∼2 months old) and aged (18 months old) C57BL/6 mice were immunized i.d. on days 0, 14, and 28 with 5 μg of trivalent split influenza virus vaccine as indicated in the legend to Fig. 1. Serum was collected, and titers of antibodies to the three strains of influenza virus vaccine were determined by ELISA. Results are reported as described in the legend to Fig. 1.

Mimi Guebre-Xabier, et al. J Virol. 2004 July;78(14):7610-7618.
5.
FIG. 2.

FIG. 2. From: Immunostimulant Patch Enhances Immune Responses to Influenza Virus Vaccine in Aged Mice.

LT-IS patch enhances secondary responses to influenza virus vaccine delivered by i.m. injection. Young (∼2 months old) and aged (18 months old) C57BL/6 mice were immunized i.m. on days 0, 14, and 28 with 5 μg of trivalent split influenza virus vaccine as indicated in the legend to Fig. 1. Serum was collected, and titers of antibodies to the three strains of influenza virus vaccine were determined by ELISA. Results are reported as described in the legend to Fig. 1.

Mimi Guebre-Xabier, et al. J Virol. 2004 July;78(14):7610-7618.
6.
Fig 6

Fig 6. From: An MDCK Cell Culture-Derived Formalin-Inactivated Influenza Virus Whole-Virion Vaccine from an Influenza Virus Library Confers Cross-Protective Immunity by Intranasal Administration in Mice.

Cross-protection against and in vivo clearance of a different subtype of influenza virus in immunized mice. (A) Mice (5 per group) were inoculated intranasally twice with PBS (no Vaccine) or with 3 μg of formalin-inactivated whole-virion vaccine from MDCK cell-adapted Vac-3 P22 (Vaccine). Fourteen days after the final immunization, the mice were infected with 107 PFU of A/Brisbane/59/2007 (BR/59/07) (H1N1), and mortality status was assessed. (B) Mice (5 per group) were inoculated intranasally with PBS (no Vaccine) or 3 μg of formalin-inactivated whole-virion vaccine from MDCK cell-adapted Vac-3 P22 (Vaccine) and were infected with 107 PFU of BR/59/07, as described for panel A. Two days after infection, the lungs were harvested, and the numbers of PFU of BR/59/07 in the lung homogenates were assessed. Bars, means ± standard deviations for 5 mice. ∗, P < 0.05 versus the group of mice inoculated intranasally with PBS.

Ahmad M. Haredy, et al. Clin Vaccine Immunol. 2013 July;20(7):998-1007.
7.
Figure 5

Figure 5. From: Alpha-C-Galactosylceramide as an Adjuvant for a Live Attenuated Influenza Virus Vaccine.

Mice inoculated with vaccine plus adjuvant (alpha-C-GalCer) generated more influenza virus specific antibodies compared with mice inoculated with vaccine alone. A-C. Mice were inoculated with PBS or 102 PFU of the rNS1 1-73 virus with or without 1ug adjuvant for 14 days and sera was harvested. An ELISA for influenza virus specific antibodies was performed on dilutions of the sera using a secondary antibody to total IgG (A), IgG1 (B), or IgG2a (C). The results for each individual mouse are graphed. D-E. Mice were inoculated with PBS or 102 PFU of the rNS1 1-73 virus with or without 1ug adjuvant for 21 days and sera was harvested. An ELISA for influenza virus specific antibodies was performed on dilutions of the sera using a secondary antibody to total IgG (D), IgG1 (E), or IgG2a (F).

Sarah A. Kopecky-Bromberg, et al. Vaccine. ;27(28):3766.
8.
Fig 6

Fig 6. Protective effect of immunization against challenge with a lethal dose of ma-pH1N1.. From: Effect of AcHERV-GmCSF as an Influenza Virus Vaccine Adjuvant.

The body weight of mice intranasally challenged with a 10LD50 dose of mouse-adapted influenza virus (ma-pH1N1) 4 weeks after the final immunization was monitored for 12 consecutive days. (A) Percentage body weight change after challenge with a 10LD50 dose of mouse-adapted influenza virus (ma-pH1N1). Changes in body weight (n = 9 mice/group) are expressed as the mean ± SD for each group. (B) Survival rate after challenge with a 10LD50 dose of mouse-adapted influenza virus (ma-pH1N1). Crosses, mice injected with PBS; black squares, mice vaccinated with AcHERV-GmCSF; gray squares, mice vaccinated with 0.2 μg of killed vaccine; red circles, mice vaccinated with 0.2 μg of killed vaccine together with AcHERV-GmCSF; open green diamonds, mice vaccinated with 2 μg of killed vaccine. Statistical analysis performed between the +GmCSF (0.2 μg of killed vaccine) and the–GmCSF (0.2 μg of killed vaccine). Statistical analysis showed that data were significant with *p < 0.05 (two-tailed Student’s t-test).

Hyo Jung Choi, et al. PLoS One. 2015;10(6):e0129761.
9.
Figure 4

Figure 4. From: Antigenic Distance Measurements for Seasonal Influenza Vaccine Selection.

Antigenic cartography for seasonal influenza viruses in the 2009-2010 season, Northern Hemisphere. Each square represents an influenza virus isolated from the season of 2009-2010. (A) The A/Brisbane/10/2007(H3N2) is the H3N2 vaccine strain used for the 2008-2009 season; (B) The A/Brisbane/57/2007(H1N1) is the H1N1 vaccine strain used for the 2008-2009 season; (C) The B/Florida/4/2006 is the influenza B vaccine strain used for the 2008-2009 season while the B/Brisbane/60/2008 is the influenza B vaccine strain used for the 2009-2010 season.

Zhipeng Cai, et al. Vaccine. ;30(2):448-453.
10.
Figure 1

Figure 1. Design and characterization of vaccine constructs.. From: A Human Multi-Epitope Recombinant Vaccinia Virus as a Universal T Cell Vaccine Candidate against Influenza Virus.

(A) Recombinant influenza virus gene constructs (NPmix or NA-HA) were inserted at the TK locus of the Western Reserve (WR) of vaccinia virus and are driven by the synthetic early/late promoter (pE/L). The cloning vectors (shown) were introduced into the wild-type WR virus by homologous recombination and iterative plaque purification. (B) Amino acid sequences of NPmix and NA-HA recombinant influenza virus protein constructs. The backbone for the NPmix construct is influenza virus NP into which was inserted other influenza virus protein human T cell epitopes. Human T cell epitopes for influenza virus M1, NS1, NP, PB1, and PA proteins are indicated. The NA-HA construct consists of the conserved regions of H5N1 influenza virus neuraminidase (N-terminal amino acids 108–231) and hemagglutinin (C-terminal amino acids 347–511).

Alan G. Goodman, et al. PLoS One. 2011;6(10):e25938.
11.
Figure 3

Figure 3. From: Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity.

Vaccine stability as a function of vaccine strain and storage temperature. HA activities of three different inactivated influenza virus strains dried in PBS or coating solution with or without 15% trehalose. H1 = inactivated influenza A/PR/8/34 (H1N1) virus; H3 = inactivated influenza A/Aichi/68 (H3N2). B = influenza B virus. CS= coating solution. Tre=trehalose.

Yeu-Chun Kim, et al. J Control Release. ;142(2):187-195.
12.
Fig. 5

Fig. 5. From: Microneedle-based vaccines.

Antibody response to influenza vaccines in rats. Data represent a subset of those originally reported in reference [4]. (A) Antibody response to whole, inactivated influenza virus following immunization with either a high dose or low dose of vaccine. Data represent day 56 ELISA titers following immunization on day 0, day 21 and day 42. (B) Antibody response to influenza virus following immunization with either a high dose or low dose of plasmid DNA encoding influenza virus hemagglutinin. Data represent day 56 ELISA titers following immunization on day 0, day 21 and day 42. (C) Antibody response to the H1N1 strain of influenza virus following immunization with either a high dose or low dose of trivalent, split virion vaccine. Data represent day 21 ELISA titers following a single immunization. (D) Antibody response to the H3N2 strain of influenza virus following immunization with either a high dose or low dose of trivalent, split virion vaccine. Data represent day 21 ELISA titers following a single immunization.

Mark R. Prausnitz, et al. Curr Top Microbiol Immunol. ;333:369-393.
13.
FIG. 1

FIG. 1. From: Assessment of Markers of the Cell-Mediated Immune Response after Influenza Virus Infection in Frail Older Adults.

Changes in titers of antibodies to each of the three strains of virus contained in the 1994-1995 influenza virus vaccine are shown. Represented are the individual fold increases in antibody titers for the influenza virus culture-negative (○) and culture-positive (•) groups. Shown are results for the response to influenza virus vaccination and the acute- to convalescent-phase period of the influenza outbreak.

Janet E. McElhaney, et al. Clin Diagn Lab Immunol. 1998 November;5(6):840-844.
14.
FIG 2

FIG 2. From: Genetic and Antigenic Typing of Seasonal Influenza Virus Breakthrough Cases from a 2008-2009 Vaccine Efficacy Trial.

Phylogenetic trees of HA1 domain nucleic acid sequences from influenza viruses calculated with respect to the vaccine strain sequence (in bold, underlined, and dark-green type) and other reference strains (vaccine strain-homologous reference strains also in dark-green type and vaccine strain-heterologous reference strains in dark-purple type) for the four subtypes: A(H3N2) (A), A(H1N1) (B), B(Yamagata) (C), and B(Victoria) (D). (C) Note that B/Alaska/05/08 (GenBank accession no. FJ686885), B/Washington//04/08 (GenBank accession no. FJ686876), and B/Michigan/11/08 (GenBank accession no. FJ686881) are reference influenza virus strains in the B/Bangladesh/3333/07 clade. (A and C) Note that the amino acid residue substitutions that distinguished between clades containing vaccine strain-homologous and vaccine strain-heterologous reference strains are indicated in boxes. The scale bars indicate the fraction of nucleotide substitutions/nucleotide sequence length.

Serge Durviaux, et al. Clin Vaccine Immunol. 2014 March;21(3):271-279.
15.
FIG. 1.

FIG. 1. From: Influenza Virus Vaccination Induces Interleukin-12/23 Receptor ?1 (IL-12/23R?1)-Independent Production of Gamma Interferon (IFN-?) and Humoral Immunity in Patients with Genetic Deficiencies in IL-12/23R?1 or IFN-? Receptor I .

T-cell responses against the trivalent influenza virus vaccine. For proliferative responses (A), control and patient PBMCs before (white bars), 7 days after (black bars), and 28 days after (striped bars) vaccination were stimulated with the influenza virus vaccine in vitro. After 3 days, [3H]thymidine incorporation was measured. For the IFN-γ ELISPOT (B), control and patient PBMCs before (white bars), 7 days after (black bars), and 28 days after (striped bars) vaccination were stimulated with the influenza virus vaccine in anti-IFN-γ-coated ELISPOT plates. After 24 h, spots of IFN-γ-producing cells were enumerated as numbers per million cells. The correlation between IFN-γ production and T-cell proliferation is shown in the inset of panel A. Ag, antigen.

Tjitske de Boer, et al. Clin Vaccine Immunol. 2008 August;15(8):1171-1175.
16.
Fig. 4

Fig. 4. From: Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles.

Effect of coating formulation on the functional HA activity of inactivated influenza virus after diying on washed Ti plates. The effects of CMC and Lutrol on the activity of the influenza virus (1 μg viral protein) were investigated by measuring HA titers in different vaccine coating formulations after one day drying at ambient conditions: T15, T15C0.25, T15C0.5, T15C1, T15L0.5, T15L1, and T15L2. (Mean ± SD; n = 16)

Hyo-Jick Choi, et al. J Control Release. ;166(2):159-171.
17.
Figure 2

Figure 2. From: Long-term persistence of IgE anti-influenza A HIN1 virus antibodies in serum of children and adults following influenza A vaccination with subsequent H1N1 infection: a case study.

Immunoblot analysis of IgG and IgE anti-H1N1 virus antibodies.
Notes: Serum from subjects with a past history of influenza virus vaccination and H1N1 infection, influenza virus vaccine and no H1N1 infection, or unvaccinated and uninfected controls was incubated with nitrocellulose strips containing H1N1 virus vaccine antigen (see Materials and methods section). IgG (left panel) representative blot of subject vaccinated with influenza virus vaccine, and infected with H1N1 virus; development time, 10 seconds. IgE (right panel), representative blot of subject vaccinated with influenza virus vaccine and infected with H1N1 virus; development time, 7 seconds. Data represent one of two patients with similar results.
Abbreviation: Ig, immunoglobulin.

Tamar A Smith-Norowitz, et al. J Inflamm Res. 2012;5:111-116.
18.
FIG. 5.

FIG. 5. From: Immunostimulant Patch Containing Heat-Labile Enterotoxin from Escherichia coli Enhances Immune Responses to Injected Influenza Virus Vaccine through Activation of Skin Dendritic Cells.

An LT-IS patch enhances mucosal antibody responses to influenza virus in the lung. Mice (as described in the legend for Fig. 3) were immunized by i.d. injection of influenza virus vaccine and received either a PBS or a 50-μg LT patch. Lung washes were collected 3 weeks after the third immunization and analyzed for IgG (A and E), IgG1 (B and F), IgG2a (C and G), and IgA (D and H) specific for A/Panama.

Mimi Guebre-Xabier, et al. J Virol. 2003 May;77(9):5218-5225.
19.
Figure 2

Figure 2. From: A Prospective, Comparative Study of the Immune Response to Inactivated Influenza Vaccine in Pediatric Liver Transplant Recipients and Their Healthy Siblings.

Mean enzyme-linked immunosorbent spot (ELISPOT) values in response to New Caledonia (A) and Shanghai (B) influenza virus strains at baseline (prior to vaccination), after 1 dose of vaccine, and after 2 doses of vaccine in transplant recipients and their healthy siblings. SFU, spot-forming unit. *Statistically significant difference in responses between the transplant recipients and their siblings (P = .01, for the New Caledonia strain after receipt of both 1 and 2 doses of vaccine; P = .02, for Shanghai strain after receipt of 1 dose of vaccine; P = .03, for Shanghai strain after receipt of 2 doses of vaccine).

Rebecca Pellett Madan, et al. Clin Infect Dis. ;46(5):712-718.
20.
Figure 6

Figure 6. Vaccination with biopolymer encapsulated live virus protects from lethal challenge with a heterosubtypic strain of influenza virus. From: Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus.

C57Bl/6J mice (n=3 mice per group) were injected SQ with biopolymer encapsulated live influenza virus PR8 (squares) or with saline containing live influenza virus PR8 (104 TCID50) (triangles). A control group of C57Bl/6J mice (n=3) were left untreated (diamonds). Forty-five days later, mice were challenged IN with a lethal dose (0.4 TCID50) of influenza virus strain H7N7 London strain and weight loss was monitored for the next 15 days. Mice losing 30% of their initial body weight were euthanized (cross symbol).

Alina C. Boesteanu, et al. Vaccine. ;29(2):314-322.

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