Evidence map›Paper›PMID 29217375›Full record

Trial reportLancet (London, England)2018

Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.

Kayvon Modjarrad, Leyi Lin, Sarah L George, Kathryn E Stephenson, Kenneth H Eckels, Rafael A De La Barrera, Richard G Jarman, Erica Sondergaard, Janice Tennant, Jessica L Ansel and 27 more

Erratum issued 3 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
27.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02937233 phase1completednot on this map

A Phase 1, Randomized, Double-Blind Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of an Accelerated Vaccination Schedule With a Zika Virus Purified Inactivated Vaccine Plus Alum Adjuvant in Healthy Adults

TypeinterventionalSponsorKathryn StephensonRan2016 to 2018Enrolled36ConditionsZikaArmsZika Virus Purified Inactivated Vaccine, Placebo
NCT02952833 phase1completednot on this map

Phase 1, Double-blinded, Placebo-Controlled Study of the Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) Administered by the Intramuscular Route in Flavivirus Naïve Adult Subjects

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2016 to 2018Enrolled91ConditionsZika Virus InfectionArmsSaline, Zika Virus Purified Inactivated Vaccine (ZPIV)
NCT02963909 phase1completednot on this map

A Phase 1, First-in-Human, Double-blinded, Randomized, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of an Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) in Healthy Flavivirus-Naïve and Flavivirus-Primed Subjects

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2016 to 2018Enrolled75ConditionsZika Virus InfectionArmsIXIARO, Placebo, YF Vax 17D Strain, Zika Virus Purified Inactivated Vaccine (ZPIV)
3 · Its place in the literature

Who cites it

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
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  6. Article
  7. Review
  8. Emerging and Pandemic Pathogens: Lessons Learned From a Clinical Research Network.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    Review
  9. An updated review of Zika virus vaccine development.Clinical and experimental vaccine research · 2025
    Review
  10. Review
  11. Article
  12. Review
  13. Zika virus: an overview update.Current opinion in HIV and AIDS · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

62 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 7 institutions in 1 country.

Kayvon ModjarradWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Leyi LinWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Sarah L GeorgeDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA; Saint Louis VA Medical Center, Saint Louis, MO, USA.
Kathryn E StephensonCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Kenneth H EckelsWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Rafael A De La BarreraWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Richard G JarmanWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Erica SondergaardWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Janice TennantDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
Jessica L AnselCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Kristin MillsWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Michael KorenWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Merlin L RobbHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Jill BarrettEmmes Corporation, Rockville, MD, USA.
Jason ThompsonEmmes Corporation, Rockville, MD, USA.
Alison E KoselEmmes Corporation, Rockville, MD, USA.
Peter DawsonEmmes Corporation, Rockville, MD, USA.
Andrew HaleUniversity of Vermont Medical Center and Larner College of Medicine, Burlington, VT, USA.
C Sabrina TanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Stephen R WalshCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Keith E MeyerDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
James BrienDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
Trevor A CrowellHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Azra BlazevicDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
Karla MosbyDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
Rafael A LaroccaCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Peter AbbinkCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Michael BoydCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Christine A BricaultCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Anne BasilHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Melissa WalshHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Veronica TonweHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Daniel F HoftDepartment of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA; Saint Louis VA Medical Center, Saint Louis, MO, USA.
Stephen J ThomasWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Dan H BarouchCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: dbarouch@bidmc.harvard.edu.
Nelson L MichaelWalter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address: nelson.l.michael2.mil@mail.mil.
Walter Reed Army Institute of Research · USBeth Israel Deaconess Medical Center · USSaint Louis University · USHenry M. Jackson Foundation · USEmmes (United States) · USRagon Institute of MGH, MIT and Harvard · USUniversity of Vermont Medical Center · US

Funding

Harvard Clinical and Translational Science Center (UL1)UL1TR000170 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2012 to 2013
$31.4M
Diversity of Immune Responses Elicited by HIV VaccinesK23AI114381 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI STEPHENSON, KATHRYN ELAINE · 2014 to 2018
$818k
Antibody-based eradication of HIV from the CNS reservoirsR21MH112360 · NIMH · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TAN, CHEN SABRINA · 2016 to 2017
$298k
IMMUNE CONTROL OF WEST NILE VIRUS QUASISPECIES DYNAMICSK22AI104794 · NIAID · SAINT LOUIS UNIVERSITY · PI BRIEN, JAMES D · 2016 to 2017
$269k
Determine if a candidate dengue vaccine in advanced trials induces antigen-specific cellular immunity that mimics immunity after multiple infections and controls antibody-enhanced viral replicationI01BX003714 · VA · ST. LOUIS VA MEDICAL CENTER · PI GEORGE, SARAH · 2017 to 2020
–
BLRD VA I01 BX003714Intramural NIH HHS Z99 AI999999NCATS NIH HHS UL1 TR000170NIAID NIH HHS HHSN27200007NIAID NIH HHS HHSN27200020NIAID NIH HHS HHSN272201000021CNIAID NIH HHS HHSN272201000021INIAID NIH HHS HHSN272201200003INIAID NIH HHS HHSN272201300021CNIAID NIH HHS HHSN272201300021INIAID NIH HHS K22 AI104794NIAID NIH HHS K23 AI114381NIMH NIH HHS R21 MH112360
6 · The paper itself

Abstract

backgroundA safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings.

methodsWe did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233.

findingsWe enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies.

interpretationThe ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults.

fundingDepartments of the Army and Defense and National Institute of Allergy and Infectious Diseases.

Indexed as

Antibodies, NeutralizingAntibodies, ViralDouble-Blind MethodHumansViral VaccinesZika VirusAntibodies, NeutralizingAntibodies, ViralViral Vaccines

Identifiers

PMID29217375
PMCPMC5884730
OpenAlexW2772658607

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.