Immune Priming and Long-term Persistence of Memory B Cells After Inactivated Poliovirus Vaccine in Macaque Models: Support for at least 2 Doses

• Type of Material: Article
• Authors: Siddhartha Bhaumik, Emory University; Raveendra Kulkarni, Emory University; William C Weldon, Center for Disease Control and Prevention; Eduardo L Silveira, Emory University; Hasan Ahmed, Emory University; Sivaram Gunisetty, Emory University; Anmol Chandele, Emory University; Rustom Antia, Emory University; Harish Verma, World Health Organization; Roland Sutter, World Health Organization; Mark A Pallansch, Center for Disease Control and Prevention; M Steven Oberste, Center for Disease Control and Prevention; Francois Villinger, Emory University; Walter Orenstein, Emory University; Kaja Murali-Krishna, Emory University
• Language: English
• Date: 2018-11-15
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciy634
• Title of Journal or Parent Work: Clinical Infectious Diseases
• ISSN: 1058-4838
• Volume: 67
• Issue: suppl_1
• Start Page: S66
• End Page: S77
• Grant/Funding Information: This work was supported by the World Health Organization Global Polio Eradication Initiative, the Monell Foundation, and the Emory Vaccine Center, Emory University School of Medicine.
• Keywords: B-cells; Science & Technology; memory; OPEN-LABEL; ENDGAME; IMMUNOGENICITY; RANDOMIZED CONTROLLED-TRIAL; neutralizing antibodies; ERADICATION; priming; Infectious Diseases; Life Sciences & Biomedicine; SCHEDULE; ENHANCED-POTENCY; Microbiology; RESPONSES; Immunology; ANTIBODIES; POLIOMYELITIS; polio; IPV
• Research Categories: Health Sciences, Immunology

Abstract

Background As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.