Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults

  1. Flavia Camponovo
  2. Joseph J Campo
  3. Timothy Q Le
  4. Amit Oberai
  5. Christopher Hung
  6. Jozelyn V Pablo
  7. Andy A Teng
  8. Xiaowu Liang
  9. B Kim Lee Sim
  10. Said Jongo
  11. Salim Abdulla
  12. Marcel Tanner
  13. Stephen L Hoffman
  14. Claudia Daubenberger
  15. Melissa A Penny  Is a corresponding author
  1. Swiss Tropical and Public Health Institute, Switzerland
  2. Antigen Discovery Inc, United States
  3. Sanaria Inc, United States
  4. Ifakara Health Institute, United Republic of Tanzania
  5. University of Basel, Switzerland

Abstract

Tanzanian adult male volunteers were immunized by direct venous inoculation with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (PfSPZ Vaccine) and protective efficacy assessed by homologous controlled human malaria infection (CHMI). Serum immunoglobulin G (IgG) responses were analyzed longitudinally using a Pf protein microarray covering 91% of the proteome, providing first insights into naturally acquired and PfSPZ Vaccine-induced whole parasite antibody profiles in malaria pre-exposed Africans. Immunoreactivity was identified against 2,239 functionally diverse Pf proteins, showing a wide breadth of humoral response. Antibody-based immune 'fingerprints' in these individuals indicated a strong person-specific immune response at baseline, with little changes in the overall humoral immunoreactivity pattern measured after immunization. The moderate increase in immunogenicity following immunization and the extensive and variable breadth of humoral immune response observed in the volunteers at baseline suggest that pre-exposure reduces vaccine-induced antigen reactivity in unanticipated ways.

Data availability

All data analyzed during this study are included in the manuscript and supporting files, or sited accordingly when published elsewhere

Article and author information

Author details

  1. Flavia Camponovo

    Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Competing interests
    No competing interests declared.
  2. Joseph J Campo

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Joseph J Campo, is an employee of Antigen Discovery, Inc.
  3. Timothy Q Le

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Timothy Q Le, is an employee of Antigen Discovery, Inc.
  4. Amit Oberai

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Amit Oberai, is an employee of Antigen Discovery, Inc.
  5. Christopher Hung

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Christopher Hung, is an employee of Antigen Discovery, Inc.
  6. Jozelyn V Pablo

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Jozelyn V Pablo, is an employee of Antigen Discovery, Inc.
  7. Andy A Teng

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Andy A Teng, is an employee of Antigen Discovery, Inc.
  8. Xiaowu Liang

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Xiaowu Liang, is an employee of Antigen Discovery, Inc.
  9. B Kim Lee Sim

    Process Development and Manufacturing, Sanaria Inc, Rockville, United States
    Competing interests
    B Kim Lee Sim, This author is affiliated with Sanaria Inc. Sanaria manufactured PfSPZ Vaccine and PfSPZ Challenge.
  10. Said Jongo

    Interventions and Clinical Trials Unit, Bagamoyo Branch, Ifakara Health Institute, Dar es Salam, United Republic of Tanzania
    Competing interests
    No competing interests declared.
  11. Salim Abdulla

    Interventions and Clinical Trials Unit, Bagamoyo Branch, Ifakara Health Institute, Dar es Salam, United Republic of Tanzania
    Competing interests
    No competing interests declared.
  12. Marcel Tanner

    Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Competing interests
    No competing interests declared.
  13. Stephen L Hoffman

    Process Development and Manufacturing, Sanaria Inc, Rockville, United States
    Competing interests
    Stephen L Hoffman, This author is employed by Sanaria. Sanaria Inc. manufactured PfSPZ Vaccine and PfSPZ Challenge. Thus, all authors associated with Sanaria have potential conflicts of interest..
  14. Claudia Daubenberger

    University of Basel, Basel, Switzerland
    Competing interests
    No competing interests declared.
  15. Melissa A Penny

    Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
    For correspondence
    melissa.penny@unibas.ch
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4972-593X

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3_170702)

  • Melissa A Penny

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: October 26, 2019
  2. Accepted: July 10, 2020
  3. Accepted Manuscript published: July 14, 2020 (version 1)
  4. Version of Record published: July 28, 2020 (version 2)

Copyright

© 2020, Camponovo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Flavia Camponovo
  2. Joseph J Campo
  3. Timothy Q Le
  4. Amit Oberai
  5. Christopher Hung
  6. Jozelyn V Pablo
  7. Andy A Teng
  8. Xiaowu Liang
  9. B Kim Lee Sim
  10. Said Jongo
  11. Salim Abdulla
  12. Marcel Tanner
  13. Stephen L Hoffman
  14. Claudia Daubenberger
  15. Melissa A Penny
(2020)
Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults
eLife 9:e53080.
https://doi.org/10.7554/eLife.53080

Further reading

    1. Epidemiology and Global Health
    Mette Hartmann Nonboe, George Napolitano ... Elsebeth Lynge
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    Background:

    Denmark was one of the few countries where it was politically decided to continue cancer screening during the COVID-19 pandemic. We assessed the actual population uptake of mammography and cervical screening during this period.

    Methods:

    The first COVID-19 lockdown in Denmark was announced on 11 March 2020. To investigate possible changes in cancer screening activity due to the COVID-19 pandemic, we analysed data from the beginning of 2017 until the end of 2021. A time series analysis was carried out to discover possible trends and outliers in the screening activities in the period 2017–2021. Data on mammography screening and cervical screening were retrieved from governmental pandemic-specific monitoring of health care activities.

    Results:

    A brief drop was seen in screening activity right after the first COVID-19 lockdown, but the activity quickly returned to its previous level. A short-term deficit of 43% [CI –49 to –37] was found for mammography screening. A short-term deficit of 62% [CI –65 to –58] was found for cervical screening. Furthermore, a slight, statistically significant downward trend in cervical screening from 2018 to 2021 was probably unrelated to the pandemic. Other changes, for example, a marked drop in mammography screening towards the end of 2021, also seem unrelated to the pandemic.

    Conclusions:

    Denmark continued cancer screening during the pandemic, but following the first lockdown a temporary drop was seen in breast and cervical screening activity.

    Funding:

    Region Zealand (R22-A597).

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    To curb the initial spread of SARS-CoV-2, many countries relied on nation-wide implementation of non-pharmaceutical intervention measures, resulting in substantial socio-economic impacts. Potentially, subnational implementations might have had less of a societal impact, but comparable epidemiological impact. Here, using the first COVID-19 wave in the Netherlands as a case in point, we address this issue by developing a high-resolution analysis framework that uses a demographically stratified population and a spatially explicit, dynamic, individual contact-pattern based epidemiology, calibrated to hospital admissions data and mobility trends extracted from mobile phone signals and Google. We demonstrate how a subnational approach could achieve similar level of epidemiological control in terms of hospital admissions, while some parts of the country could stay open for a longer period. Our framework is exportable to other countries and settings, and may be used to develop policies on subnational approach as a better strategic choice for controlling future epidemics.