21 research outputs found
MRKAd5 HIV vaccine generated neutralizing antibodies to Ad5 capsid proteins more efficiently than to Ad5 fiber.
<p>The titers of Nab to Ad5, Ad5 F35, Ad35 and Ad35 F5 were determined in Ad5 seronegatives and Ad5 seropositives following vaccinations. The minimum detectable titer is at 1∶12 serum dilution and the maximum titer is at the end point dilution to achieve 90% neutralization of the vector. The development of Nab in baseline seronegatives (<b>A</b>) or seropositives (<b>B</b>) at 4 weeks after each vaccination was also shown. <b>A</b> (lower panel) and <b>B</b> (lower panel) show the Nab targets in these sera, excluding sera samples with high anti-Ad35 Nab titers which confound the categorization of the Nab target. (<b>C</b>) Direct comparison of the titer of Nabs to Ad5, or Ad5 capsid, or Ad5 fiber between baseline seronegatives and seropositives. Day 0: pre-vaccination; Week 4: 4 weeks after the first vaccination; Week 8: 4 weeks after the second vaccination; Week 30: 4 weeks after the third vaccination.</p
Pre-existing anti-Ad5 fiber neutralizing antibodies reduced immune responses generated by MRKAd5 HIV-1 gag/pol/nef vaccine, especially HIV specific CD8+ immune responses.
<p>Median (25%–75% percentile),</p>*<p>: p<0.05;</p>**<p>: p<0.01,</p>***<p>: p<0.001.</p
Seroprevalence of Ad35 in HIV-infected, Ad5 seropositive participants is lower compared to that in HIV-uninfected, Ad5 seropositive participants.
*<p>values used for Fisher's exact test, p = 0.002.</p
Pre-existing anti-Ad5 capsid neutralizing antibodies reduced immune responses generated by MRKAd5 HIV-1 gag/pol/nef vaccine, especially HIV-specific CD8+ immune responses.
<p>Median (25%–75% percentile),</p>*<p>: p<0.05;</p>**<p>: p<0.01,</p>***<p>: p<0.001.</p
Pre-existing anti-Ad5 neutralizing antibodies reduced immune responses generated by MRKAd5 HIV-1 gag/pol/nef vaccine, especially HIV-specific CD8+ immune responses.
<p>Median (25%–75% percentile),</p>*<p>: p<0.05;</p>**<p>: p<0.01,</p>***<p>: p<0.001.</p
Seroprevalence of Ad14, Ad28 and Ad41 in HIV-infected, Ad5 seropositive and HIV-uninfected, Ad5 seropositive participants is similar.
*<p>Fisher's exact test.</p
Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults
<div><p>Background</p><p>A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV).</p><p>Methods</p><p>20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3–17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.</p><p>Results</p><p>Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.</p><p>Conclusions</p><p>H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00973895" target="_blank">NCT00973895</a></p></div
Immunogenicity.
<p>(A) Hemagglutination Inhibition (HAI) assay with A/Mexico/4482/2009 H1N1 virus (B) Neutralizing antibodies were evaluated by the capacity of sera to prevent infection of 293A cells by replication-incompetent H1-pseudotyped virus. The 80% inhibition serum titers are shown. (C) End-point ELISA titers of H1 A/California/04/2009(H1N1) specific antibodies are shown. Pre-vaccination titers have been subtracted from each plotted value. (D) H1-specific T cell responses are shown as a number of spot forming cells (SFC) per 10<sup>6</sup> PBMC as measured by ELISpot assay. Geometric means and 95% CI are shown for the study groups.</p
Rapid DNA Vaccine Manufacturing in Response to Influenza Pandemic.
<p>Rapid DNA Vaccine Manufacturing in Response to Influenza Pandemic.</p
Consort Flow Diagram.
<p>Number of individuals assessed for eligibility, enrolled and followed up.</p