Dose-dependent protective efficacy of H5N1 vaccine-induced immune sera in mice.

<p>Shown are reciprocal MN titers:</p>a<p>expected titer based on the volume and titer of injected immune sera;</p>b<p>measured circulating titer 2 h prior to challenge;</p>c<p>extrapolated from titers measured 2 h prior to challengea.</p>d<p>Mice were challenged intranasally with 10⁴ TCID₅₀ wild-type H5N1 virus. Animals surviving for ≥14 days are considered protected.</p>e<p>Immune serum administered on 3 successive days. n.a., not applicable.</p

Correlation of survival of passively immunized mice with neutralizing antibody titer following challenge with wild-type H5N1 virus.

<p>Data points represent the mean % of surviving animals 14 days following lethal challenge of CD1 mice which had received immune sera from (<b>A</b>) CD1 mice, (<b>B</b>) guinea pigs or (<b>C</b>) humans. Reciprocal neutralizing antibody titers shown are extrapolated from titers measured 2 h prior to challenge. All individual mice receiving mouse immune sera of titer ≥1∶18 or guinea pig immune sera of titer ≥1∶37 were protected from disease; these animals are omitted from the figure to allow better resolution of lower titers.</p

ROC curve analysis of four immunological assays.

<p>Assays were evaluated for their ability to discriminate non-infected from infected mice in challenge experiments using (<b>A</b>) <i>B. burgdorferi</i> s.s. and (<b>B</b>) <i>B. afzelii</i>. Area under the curve (AUC) values are included.</p

Antibody GMTs in infected and non-infected mice; sensitivity, specificity, AUC and maximum Youden Index for each assay; and cutoff titers derived from the Youden Index which could be used as correlates of protection.

<p>Antibody GMTs in infected and non-infected mice; sensitivity, specificity, AUC and maximum Youden Index for each assay; and cutoff titers derived from the Youden Index which could be used as correlates of protection.</p

GMT antibody titers and protection of vaccinated mice against challenge with <i>B. burgdorferi</i> s.s. and <i>B. afzelii</i>.

<p>GMT antibody titers and protection of vaccinated mice against challenge with <i>B. burgdorferi</i> s.s. and <i>B. afzelii</i>.</p

Correlation of immunological assays with rOspA-1/2 vaccine-induced protective efficacy.

<p>Serum antibody titers quantified by ELISA, CI-ELISA, SB assay and killing assay are shown for OspA-1/2-immunized mice which were either protected from or infected by (<b>A</b>) needle challenge with <i>B. burgdorferi s.s.</i> strain ZS7 or (<b>B</b>) tick challenge with <i>B. afzelii</i>. Shown are the geometric mean titers of each group as well as individual serum titers. P values represent the strength of the correlation of assay titers with protective efficacy as calculated by the Mann-Whitney U test. Two serum samples were unavailable for evaluation in the <i>B. burgdorferi</i> s.s CI and killing assays; one serum sample was unavailable for evaluation in the <i>B. afzelii</i> CI assay.</p

Protective efficacy of MVA vectors in Balb/c mice.

<p>Data are n/N (%) protected mice, 14 days after challenge with with 42 LD₅₀ of H5N1 VN1203, 32 LD₅₀ of mouse-adapted H9N2 HK/G9 or 16 LD₅₀ of H7N1 RO/34.</p>a<p>mice were immunologically primed by infecting with H1N1 six weeks prior to immunization.</p

Weight loss after H5N1, H9N2 and H7N1 challenge.

<p>Mice were immunized twice, three weeks apart, with MVA vectors and challenged three weeks later with (<b>A and B</b>) 42 LD₅₀ of H5N1 VN1203, (<b>C</b>) 32 LD₅₀ of mouse-adapted H9N2 HK/G9 or (<b>D</b>) 16 LD₅₀ of H7N1 RO/34. (<b>B</b>) Primed mice were infected intranasally with 100 TCID₅₀ H1N1pdm09 virus, six weeks before immunization. Animals were monitored for 14 days after challenge. Shown are the daily variations in weight, as percentages compared to before virus challenge.</p

Symptom scores after H5N1, H9N2 and H7N1 challenge.

<p>Mice were immunized twice, three weeks apart, with MVA vectors and challenged three weeks later with (<b>A and B</b>) 42 LD₅₀ of H5N1 VN1203, (<b>C</b>) 32 LD₅₀ of mouse-adapted H9N2 HK/G9 or (<b>D</b>) 16 LD₅₀ of H7N1 RO/34. (<b>B</b>) Primed mice were infected intranasally with 100 TCID₅₀ H1N1pdm09 virus, six weeks before immunization. Animals were monitored for 14 days after challenge. Shown are the cumulative mean symptom scores whereby ruffled fur, curved posture, apathy and death were scored as 1, 2, 3 and 4, respectively.</p

Conserved M2e sequences used to generate quadrivalent M2e coding sequence.

a<p>Example of a specific virus strain coding the respective M2e sequence.</p>b<p>Amino acid sequence of the respective M2e. Differences to the H5N1 M2e sequence are highlighted in bold.</p>C<p>Amino acid sequence of H1N1 is identical to that of H2N2 A/Korea/426/68 and H3N2 A/NewYork/392/2004.</p