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DNA and rAd5 including regimens induce distinct antibody profiles.

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posted on 2021-11-29, 18:52 authored by Stephanie Fischinger, Deniz Cizmeci, Davy Deng, Shannon P. Grant, Nicole Frahm, Julie McElrath, Jonathan Fuchs, Pierre-Alexandre Bart, Giuseppe Pantaleo, Michael Keefer, William O. Hahn, Nadine Rouphael, Gavin Churchyard, Zoe Moodie, Yeycy Donastorg, Hendrik Streeck, Galit Alter

Multivariate analysis of antibody profiles using 69 features for each plasma sample was performed. A: An unsupervised principal component analysis (PCA) was first used and demonstrates the separation of the different vaccine trials based on their antibody profiles. Each dot represents one vaccinated individual at peak immunogenicity and the colors indicate the trial arm as depicted in the legend. Next using a supervised PLSDA, differences in antibody profiles was examined in: B: DNA containing regimens (HVTN 077 T2, T3; 105 T1, T2, T3; 204; 205 T3) versus trials which do not incorporate DNA in their vaccine regimen (HVTN 077 T1; 078; 105 T3; 205 T4)- with a model accuracy of 77.3%; C: protein containing regimens (HVTN 105 all arms) compared to non-protein containing immunizations (HVTN 077, 078, 204, 205, all arms), with a model accuracy of 75.8%; and D: DNA/rAd containing regimens (HVTN 077 T2, T3; 204) versus all other regimens (HVTN 078, 105, 205) -with a model accuracy of 90.7%. E and F show the antibody features that were differed most significantly across the vaccine groups, ranked based on their Variable in Projection Score (VIP). Features are color coded based on the vaccine group in which they were enriched. E: variables pointing to the left (dark green) are enriched in vaccines without a protein component whereas features pointing to the right are increased in protein vaccine trials (light green). F: Features that point to the left were enriched in DNA + rAd5/rAd35 trials (blue), while those ordered on the right side are enhanced in other vaccine regimen trials (pink).

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