Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially Affected by Vaccine Vectors

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Aug 16

PMID 30110638

Citations 9

Authors

Michelle Meyer

Asuka Yoshida

Palaniappan Ramanathan

Erica Ollmann Saphire

Peter L Collins

James E Crowe Jr

Siba Samal

Alexander Bukreyev

Affiliations

Soon will be listed here.

Abstract

Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes. While an immunogen determines the breadth of antibody response, distinct vaccine vectors can induce qualitatively different responses, affecting protective efficacy. These data suggest that immune correlates of vaccine protection cannot be generalized for all vaccines against the same pathogen, even if they use the exact same immunogen.

Citing Articles

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References

Schone D, Hrycak C, Windmann S, Lapuente D, Dittmer U, Tenbusch M . Immunodominance of Adenovirus-Derived CD8 T Cell Epitopes Interferes with the Induction of Transgene-Specific Immunity in Adenovirus-Based Immunization. J Virol. 2017; 91(20). PMC: 5625516. DOI: 10.1128/JVI.01184-17. View

Bukreyev A, Yang L, Zaki S, Shieh W, Rollin P, Murphy B . A single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose Ebola virus challenge. J Virol. 2006; 80(5):2267-79. PMC: 1395378. DOI: 10.1128/JVI.80.5.2267-2279.2006. View

Dowling W, Thompson E, Badger C, Mellquist J, Garrison A, Smith J . Influences of glycosylation on antigenicity, immunogenicity, and protective efficacy of ebola virus GP DNA vaccines. J Virol. 2006; 81(4):1821-37. PMC: 1797596. DOI: 10.1128/JVI.02098-06. View

Martinez O, Tantral L, Mulherkar N, Chandran K, Basler C . Impact of Ebola mucin-like domain on antiglycoprotein antibody responses induced by Ebola virus-like particles. J Infect Dis. 2011; 204 Suppl 3:S825-32. PMC: 3189980. DOI: 10.1093/infdis/jir295. View

Kennedy S, Bolay F, Kieh M, Grandits G, Badio M, Ballou R . Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017; 377(15):1438-1447. PMC: 5705229. DOI: 10.1056/NEJMoa1614067. View

Bukreyev A, Marzi A, Feldmann F, Zhang L, Yang L, Ward J . Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge. Virology. 2008; 383(2):348-61. PMC: 2649782. DOI: 10.1016/j.virol.2008.09.030. View

Wakamatsu N, King D, Seal B, Peeters B, Brown C . The effect on pathogenesis of Newcastle disease virus LaSota strain from a mutation of the fusion cleavage site to a virulent sequence. Avian Dis. 2007; 50(4):483-8. DOI: 10.1637/7515-020706R.1. View

Alexander D . Newcastle disease and other avian paramyxoviruses. Rev Sci Tech. 2000; 19(2):443-62. DOI: 10.20506/rst.19.2.1231. View

Marzi A, Engelmann F, Feldmann F, Haberthur K, Shupert W, Brining D . Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proc Natl Acad Sci U S A. 2013; 110(5):1893-8. PMC: 3562844. DOI: 10.1073/pnas.1209591110. View

10.

Sanchez A, Kiley M, Holloway B, Auperin D . Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. 1993; 29(3):215-40. DOI: 10.1016/0168-1702(93)90063-s. View

11.

Shedlock D, Bailey M, Popernack P, Cunningham J, Burton D, Sullivan N . Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms. Virology. 2010; 401(2):228-35. PMC: 3351102. DOI: 10.1016/j.virol.2010.02.029. View

12.

Lee J, Kuehne A, Abelson D, Fusco M, Hart M, Saphire E . Complex of a protective antibody with its Ebola virus GP peptide epitope: unusual features of a V lambda x light chain. J Mol Biol. 2007; 375(1):202-16. PMC: 2173910. DOI: 10.1016/j.jmb.2007.10.017. View

13.

Subbiah M, Khattar S, Collins P, Samal S . Mutations in the fusion protein cleavage site of avian paramyxovirus serotype 2 increase cleavability and syncytium formation but do not increase viral virulence in chickens. J Virol. 2011; 85(11):5394-405. PMC: 3094964. DOI: 10.1128/JVI.02696-10. View

14.

Towner J, Paragas J, Dover J, Gupta M, Goldsmith C, Huggins J . Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology. 2005; 332(1):20-7. DOI: 10.1016/j.virol.2004.10.048. View

15.

Kusagawa S, Komada H, Mao X, Kawano M, NISHIKAWA F, Tsurudome M . Antigenic and molecular properties of Murayama virus isolated from cynomolgus monkeys: the virus is closely related to avian paramyxovirus type 2. Virology. 1993; 194(2):828-32. DOI: 10.1006/viro.1993.1325. View

16.

Takada A, Ebihara H, Feldmann H, Geisbert T, Kawaoka Y . Epitopes required for antibody-dependent enhancement of Ebola virus infection. J Infect Dis. 2007; 196 Suppl 2:S347-56. DOI: 10.1086/520581. View

17.

Flyak A, Shen X, Murin C, Turner H, David J, Fusco M . Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection. Cell. 2016; 164(3):392-405. PMC: 4733404. DOI: 10.1016/j.cell.2015.12.022. View

18.

Biacchesi S, Pham Q, Skiadopoulos M, Murphy B, Collins P, Buchholz U . Modification of the trypsin-dependent cleavage activation site of the human metapneumovirus fusion protein to be trypsin independent does not increase replication or spread in rodents or nonhuman primates. J Virol. 2006; 80(12):5798-806. PMC: 1472577. DOI: 10.1128/JVI.00294-06. View

19.

Volchkova V, Feldmann H, Klenk H, Volchkov V . The nonstructural small glycoprotein sGP of Ebola virus is secreted as an antiparallel-orientated homodimer. Virology. 1998; 250(2):408-14. DOI: 10.1006/viro.1998.9389. View

20.

Chandran K, Sullivan N, Felbor U, Whelan S, Cunningham J . Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science. 2005; 308(5728):1643-5. PMC: 4797943. DOI: 10.1126/science.1110656. View