Format

Send to

Choose Destination
Hum Vaccin Immunother. 2019 Oct 7:1-12. doi: 10.1080/21645515.2019.1654807. [Epub ahead of print]

Combining immunoprofiling with machine learning to assess the effects of adjuvant formulation on human vaccine-induced immunity.

Author information

1
Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command , Fort Detrick , MD , USA.
2
Malaria Vaccine Branch, U.S. Military Malaria Research Program, Walter Reed Army Institute of Research , Silver Spring , MD , USA.
3
Department of Bacterial and Parasitic Diseases, AFRIMS, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok , Thailand.
4
Basic Immunology Branch/DAIT/NIAID/NIH , Rockville , MD , USA.

Abstract

Adjuvants produce complex, but often subtle, effects on vaccine-induced immune responses that, nonetheless, play a critical role in vaccine efficacy. In-depth profiling of vaccine-induced cytokine, cellular, and antibody responses ("immunoprofiling") combined with machine-learning holds the promise of identifying adjuvant-specific immune response characteristics that can guide rational adjuvant selection. Here, we profiled human immune responses induced by vaccines adjuvanted with two similar, clinically relevant adjuvants, AS01B and AS02A, and identified key distinguishing characteristics, or immune signatures, they imprint on vaccine-induced immunity. Samples for this side-by-side comparison were from malaria-naïve individuals who had received a recombinant malaria subunit vaccine (AMA-1) that targets the pre-erythrocytic stage of the parasite. Both adjuvant formulations contain the same immunostimulatory components, QS21 and MPL, thus this study reveals the subtle impact that adjuvant formulation has on immunogenicity. Adjuvant-mediated immune signatures were established through a two-step approach: First, we generated a broad immunoprofile (serological, functional and cellular characterization of vaccine-induced responses). Second, we integrated the immunoprofiling data and identify what combination of immune features was most clearly able to distinguish vaccine-induced responses by adjuvant using machine learning. The computational analysis revealed statistically significant differences in cellular and antibody responses between cohorts and identified a combination of immune features that was able to distinguish subjects by adjuvant with 71% accuracy. Moreover, the in-depth characterization demonstrated an unexpected induction of CD8+ T cells by the recombinant subunit vaccine, which is rare and highly relevant for future vaccine design.

KEYWORDS:

Apical Membrane Antigen; Immunoprofile; Plasmodium falciparum; adjuvant; protection; vaccine

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center