title: Specific neutralizing response in plasma from convalescent patients of Ebola Virus Disease against the West Africa Makona variant of Ebola virus.
abstract: BACKGROUND
  The current outbreak of Ebola Virus Disease in West Africa is caused by a new variant of Ebola virus (EBOV) named Makona 2014, whose sequence differs 3% from isolates from Central Africa such as Mayinga 1976 EBOV. The specificity and kinetics of the neutralizing antibody response induced by the circulating Makona EBOV has not been thoroughly studied.
  
  
  METHODS
  We have used a lentiviral EBOV-glycoprotein (GP)-pseudotyped infection assay to measure Makona-GP and Mayinga-GP specific neutralizing activity of plasma from three convalescent Ebola Virus Disease patients from the current EBOV outbreak at 2, 3, 4 and 9 months post-infection. Total anti-EBOV GP IgG was measured by a commercial ELISA assay.
  
  
  RESULTS
  In convalescent Ebola Virus Disease patients, Makona-GP-specific neutralizing titers increased from 2 months (mean IC50 1/59), 3 months (IC50 1/212), 4 months (IC50 1/239) and up to 9 months (IC50 1/268) post-infection. Neutralizing activity of plasma from the three convalescent Ebola Virus Disease patients was more vigorous against the current Makona-GP pseudotyped EBOV variant than against Mayinga-GP pseudotyped EBOV and this difference was observed at each time point tested: Mayinga vs Makona mean IC50 fold=4.92 at 2 months post-infection, 2.89 fold at 3 months post-infection, 2.23 at 4 months post-infection and 2.98 at 9 months post-infection (all differences p<0.01). Total level of IgG against EBOV-GP did not evolve significantly during the follow up.
  
  
  CONCLUSIONS
  In convalescent Ebola Virus Disease patients, EBOV-GP specific neutralizing activity increases over time, at least up to 9 months post-infection, which suggests that active affinity maturation of antibodies takes place long after clinical recovery. EBOV-GP specific neutralizing response is significantly higher against Makona EBOV circulating in West Africa than against the variants included in the currently approved vaccines. Correlates of protection for EBOV vaccines have not been completely established and the relevance of a lower neutralizing activity in convalescent plasma from the current outbreak against one of the EBOV-GPs contained in the vaccines in terms of its potential efficacy does not necessarily preclude its efficacy. However, this observation highlights the concern regarding the natural diversity of EBOV and its subsequent challenge for diagnosis, therapy and vaccine design. EBOV-GP neutralizing activity varies considerably over time in convalescent Ebola Virus Disease patients. Titering of convalescent blood products would be desirable to standardize and evaluate their potential therapeutic value.
authors.affiliation: Department of Microbiology, Instituto de Investigación Hospital 12 de Octubre (imas12), CAA, Avenida de Córdoba sn, 28041 Madrid, Spain. Electronic address: joanna.luczkowiak@gmail.com.
authors.forename: Joanna
authors.initials: J
authors.lastname: Luczkowiak
authors.affiliation: Infectious Diseases Unit, Department of Internal Medicine, Instituto de Investigación Hospital La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046 Madrid, Spain. Electronic address: joser.arribas@salud.madrid.org.
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: Department of Microbiology, Instituto de Investigación Hospital 12 de Octubre (imas12), CAA, Avenida de Córdoba sn, 28041 Madrid, Spain. Electronic address: alkalimme@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Gómez
authors.affiliation: Department of Hematology, Instituto de Investigación Hospital La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046 Madrid, Spain. Electronic address: vjyuste@gmail.com.
authors.forename: Víctor
authors.initials: V
authors.lastname: Jiménez-Yuste
authors.affiliation: Tropical Diseases Unit, Department of Internal Medicine, Instituto de Investigación Hospital La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046 Madrid, Spain. Electronic address: fercalleprieto@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Calle
authors.affiliation: Department of Hematology, Instituto de Investigación Hospital La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046 Madrid, Spain. Electronic address: aurora.viejo@salud.madrid.org.
authors.forename: Aurora
authors.initials: A
authors.lastname: Viejo
authors.affiliation: Department of Microbiology, Instituto de Investigación Hospital 12 de Octubre (imas12), CAA, Avenida de Córdoba sn, 28041 Madrid, Spain. Electronic address: rafael.delgado@madrid.salud.org.
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado
mesh_terms: D000350:Africa, Central; D000354:Africa, Western; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D029043:Ebolavirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D020128:Inhibitory Concentration 50; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G
keywords: Ebola Virus Disease; Makona Ebola virus; Mayinga Ebola virus; convalescent patients; neutralization assay