Evidence map›Paper›PMID 31525197›Full record

ArticlePLoS neglected tropical diseases2019

Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans.

Parakkal Jovvian George, Jessica A Hess, Sonia Jain, John B Patton, Tingting Zhan, Nancy Tricoche, Bin Zhan, Maria Elena Bottazzi, Peter J Hotez, David Abraham and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Parakkal Jovvian GeorgeLaboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, New York, United States of America.ORCID 0000-0002-9847-6829
Jessica A HessDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Sonia JainLaboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
John B PattonDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Tingting ZhanDivision of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Nancy TricocheLaboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
Bin ZhanTexas Children's Hospital Center for Vaccine Development, Departments of Pediatric Tropical Medicine and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Maria Elena BottazziTexas Children's Hospital Center for Vaccine Development, Departments of Pediatric Tropical Medicine and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Peter J HotezTexas Children's Hospital Center for Vaccine Development, Departments of Pediatric Tropical Medicine and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
David AbrahamDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Sara LustigmanLaboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
New York Blood Center · USThomas Jefferson University · USBaylor College of Medicine · US

Funding

The development of a recombinant vaccine against human onchocerciasisR01AI078314 · NIAID · NEW YORK BLOOD CENTER · PI LUSTIGMAN, SARA · 2009 to 2021
$7.0M
NIAID NIH HHS R01 AI078314
6 · The paper itself

Abstract

backgroundThe current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection. METHODOLOGY/PRINCIPAL

findingsProtection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not protected from an Onchocerca volvulus challenge. To determine a possible association between antigen-specific antibody responses and anti-larvae protective immunity in humans, we analyzed the presence of anti-Ov-103 and anti-Ov-RAL-2 cytophilic antibody responses (IgG1 and IgG3) in individuals classified as putatively immune, and in infected individuals who developed concomitant immunity with age. It was determined that 86% of putatively immune individuals and 95% individuals with concomitant immunity had elevated IgG1 and IgG3 responses to Ov-103 and Ov-RAL-2. Based on the elevated chemokine levels associated with protection in the Ov-103 or Ov-RAL-2 immunized mice, the profile of these chemokines was also analyzed in putatively immune and infected individuals; both groups contained significantly higher levels of KC, IP-10, MCP-1 and MIP-1β in comparison to normal human sera. Moreover, human monospecific anti-Ov-103 antibodies but not anti-Ov-RAL-2 significantly inhibited the molting of third-stage larvae (L3) in vitro by 46% in the presence of naïve human neutrophils, while both anti-Ov-103 and anti-Ov-RAL-2 antibodies significantly inhibited the molting by 70-80% when cultured in the presence of naive human monocytes. Interestingly, inhibition of molting by Ov-103 antibodies and monocytes was only in part dependent on contact with the cells, while inhibition of molting with Ov-RAL-2 antibodies was completely dependent on contact with the monocytes. In comparison, significant levels of parasite killing in Ov-103 and Ov-RAL-2 vaccinated mice only occurred when cells enter the parasite microenvironment. Taken together, antibodies to Ov-103 and Ov-RAL-2 and cells are required for protection in mice as well as for the development of immunity in humans. CONCLUSIONS/SIGNIFICANCE: Alum-adjuvanted Ov-103 and Ov-RAL-2 vaccines have the potential of reducing infection and thus morbidity associated with onchocerciasis in humans. The development of cytophilic antibodies, that function in antibody-dependent cellular cytotoxicity, is essential for a successful prophylactic vaccine against this infection.

Indexed as

Immunogenicity, VaccineAdjuvants, ImmunologicAlum CompoundsAnimalsAntibodies, HelminthAntigens, HelminthChemokinesImmunoglobulin GLarvaMaleMiceMice, Inbred C57BLMonocytesOnchocerca volvulusOnchocerciasisVaccinationAdjuvants, ImmunologicAlum Compoundsaluminum sulfateAntibodies, HelminthAntigens, HelminthChemokinesImmunoglobulin GVaccines

Identifiers

PMID31525197
PMCPMC6762197
OpenAlexW2974388666

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LicenceCC BY
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Registered trials

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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.