title: Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus.
abstract: The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine.
  
  
  
  199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation.
  
  
  
  An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus.
  
  
  
  Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Ayan
authors.initials: A
authors.lastname: Dey
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Molodecky
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Harish
authors.initials: H
authors.lastname: Verma
authors.affiliation: International Vaccine Institute, Seoul, South Korea.|Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Saletti
authors.affiliation: World Health Organization- National Polio Surveillance Project, New Dehli, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: World Health Organization- National Polio Surveillance Project, New Dehli, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Bahl
authors.affiliation: International Vaccine Institute, Seoul, South Korea.|Vaccine Development Global Program, PATH, Washington, DC, United States of America.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
authors.affiliation: National institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Ranjan K
authors.initials: RK
authors.lastname: Nandy
authors.affiliation: Enterovirus Research Centre, Mumbai, India.
authors.forename: Jagadish M
authors.initials: JM
authors.lastname: Deshpande
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Roland W
authors.initials: RW
authors.lastname: Sutter
authors.affiliation: International Vaccine Institute, Seoul, South Korea.|Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Nice-Sophia Antipolis, Valbonne, France.
authors.forename: Cecil
authors.initials: C
authors.lastname: Czerkinsky
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005243:Feces / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D017063:Outcome Assessment, Health Care / Q000379:methods; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D017955:Poliovirus / Q000145:classification / Q000276:immunology*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000276:immunology; D011379:Prognosis; D015203:Reproducibility of Results; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011054:Poliovirus Vaccine, Inactivated; D011055:Poliovirus Vaccine, Oral