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

Abstract

BackgroundAs 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.MethodsWe 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.ResultsA 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.ConclusionsTwo doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

“…For example, Bhaumik et al investigated the long-term persistence of immune memory following oneor two-dose inactivated poliovirus vaccine schedules. They showed that memory B cells can be induced by both vaccine regimens, although this cell subset declined by five months after a single immunization, whereas it persisted for more than one year with the twodose strategy [59]. Additionally, identifying predictive biomarkers at baseline, i.e., before vaccination, has drawn interest from researchers who reported proof-of-concept results on influenza [60,61], yellow fever [62], and hepatitis B [63] vaccines.…”

“…Additionally, preclinical models are often instrumental in appraising long-term immune memory, as longitudinal studies can be initiated and conducted more easily and rapidly than in human populations. For example, NHPs have been successfully used to study memory responses induced by vaccines against SIV, tuberculosis, and or polio [59,[217][218][219]. Implementing systems vaccinology techniques in prolonged longitudinal preclinical studies [72] could link initial and long-term responses and generate early signatures of immune memory.…”

Medical, Genomic, and Evolutionary Aspects of the Peptide Sharing between Pathogens, Primates, and Humans

“… 1 2 3 4 5 6 7 8 9 10 11 12 Such cross-reactivity is not evident in experimental infections of primates. 13 Actually, following preclinical studies performed in primates 14 15 16 17 18 as recommended by the Food and Drug Administration, 19 the reports declare that primate active immunization by pathogen vaccine administration is well tolerated and exempt of relevant events. Hence, the questions: why the potential cross-reactivity and the consequent potential autoimmune sequelae do not occur in primates following experimental infections or during preclinical tests?…”

Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study

“…IPV and OPV are both effective in preventing polio disease. However, the use of OPV can cause rare cases of vaccine-associated paralytic poliomyelitis, as well as a significant resurgence of poliomyelitis cases due to circulating vaccine-derived poliovirus [ 8 , 9 ] and low vaccination coverage in some countries [ 10 , 11 ]. For this reason, the core of the Polio Eradication and Endgame Strategic Plan implemented by the Global Polio Eradication Initiative is to introduce IPV into routine immunization programs worldwide, as a replacement for OPV [ 2 , 12 , 13 ].…”