Novel oral polio vaccine for serotype 2: new hope
Authors: Poonam Mathur, Shyam Kottilil
Journal: The Lancet Infectious Diseases (2023)

Poliomyelitis, a debilitating disease, has been largely eliminated due to the global dissemination of effective vaccines. The first vaccine against poliovirus, introduced in 1961, was a trivalent oral polio vaccine (OPV) against serotypes 1–3. Vaccination campaigns with trivalent OPVs eventually led to the eradication of serotype 2 in 2015.1US Centers for Disease Control and PreventionPolio disease and poliovirus containment.https://www.cdc.gov/orr/polioviruscontainment/diseaseandvirus.htmDate: 2022Date accessed: August 18, 2023Google Scholar Vaccination campaigns then shifted to bivalent OPVs (bOPVs), conferring protection against serotypes 1 and 3 only.1US Centers for Disease Control and PreventionPolio disease and poliovirus containment.https://www.cdc.gov/orr/polioviruscontainment/diseaseandvirus.htmDate: 2022Date accessed: August 18, 2023Google Scholar A consequence of this change was the emergence of circulating vaccine-derived poliovirus 2 (cVDPV2). cVDPV2 is a result of virus excretion from an individual immunised with an OPV and low population immunity against the poliovirus serotype. cVDPV2 is capable of human-to-human transmission and neurovirulence, causing paralysis in patients. After the shift to bOPV for vaccination campaigns in 2016, the predominant strain for circulating vaccine-derived poliovirus (causing 95% of cases) is serotype 2. cVDPV2 has been flagged as a concerning source of polio outbreaks.2Lai YA Chen X Kunasekaran M Rahman B MacIntyre CR Global epidemiology of vaccine-derived poliovirus 2016-2021: a descriptive analysis and retrospective case-control study.EClinicalMedicine. 2022; 50101508Summary Full Text Full Text PDF Scopus (10) Google Scholar To overcome the public health threat of cVDPV2, the Salk inactivated polio vaccine (IPV), developed in 1955, was incorporated into immunisation schedules since it provides humoral immunity against all three poliovirus types and reduces the risk of paralytic poliomyelitis.3Polio Global Eradrication InitativeInactivated polio vaccine now introduced worldwide.https://polioeradication.org/news-post/inactivated-polio-vaccine-now-introduced-worldwide/Date: 2019Date accessed: August 18, 2023Google Scholar Despite the global availability of IPV since 2019, outbreaks of cVDPV2 persist.2Lai YA Chen X Kunasekaran M Rahman B MacIntyre CR Global epidemiology of vaccine-derived poliovirus 2016-2021: a descriptive analysis and retrospective case-control study.EClinicalMedicine. 2022; 50101508Summary Full Text Full Text PDF Scopus (10) Google Scholar In these cases, the Sabin monovalent OPV against serotype 2 (mOPV2) has been used for rapid vaccination, but since it is a live virus, it carries the risk of vaccine-associated paralytic poliomyelitis. The novel OPV for serotype 2 (nOPV2) was genetically engineered to be more resistant to mutation and revision to neurovirulence than the mOPV2.4Macklin GR Peak C Eisenhawer M et al.Enabling accelerated vaccine roll-out for Public Health Emergencies of International Concern (PHEICs): novel oral polio vaccine type 2 (nOPV2) experience.Vaccine. 2023; 41: 122-127Crossref PubMed Scopus (26) Google Scholar The nOPV2 is the first vaccine authorised by WHO in the emergency use listing procedure, which recommends two doses of nOPV2 4 weeks apart in an outbreak scenario. This procedure could be logistically limiting in an outbreak, with risk for loss-to-follow-up due to a large time interval between doses and difficulty in accessing health-care centres for dosing. Therefore, the study by Luis Rivera Mejia and colleagues5Rivera Mejía L Peña Méndez L Bandyopadhyay AS et al.Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican Republic.Lancet Infect Dis. 2023; (published online Dec 15.)https://doi.org/10.1016/S1473-3099(23)00519-4Summary Full Text Full Text PDF Scopus (2) Google Scholar sought to assess if a shorter nOPV2 vaccination schedule is non-inferior to the current procedure for hypothetical use in an outbreak. The study enrolled 905 healthy infants in the Dominican Republic who were randomly allocated (1:1:1) to receive two doses of nOPV2 1 week apart, 2 weeks apart, or 4 weeks apart (standard of care). The investigators found non-inferiority of safety and immunogenicity for two nOPV2 doses 2 weeks apart (difference in rates –3·7; 95% CI –7·9 to 0·3), supporting the use of a modified nOPV2 vaccination schedule for infants in the event of an outbreak. However, non-inferiority was not shown for the 1-week schedule (–8·0; –12·7 to –3·6), indicating this interval between the 2 doses of nOPV did not confer similar immunogenicity as the standard of care. The results of this study are highly important since this dosing schedule confers immunity against poliovirus 2, with increased dosing flexibility as part of an outbreak response. However, some questions remain on how this dosing schedule affects intestinal immunity, immunogenicity to other vaccinations, and herd immunity. WHO recommends 3 bOPVs as a primary series. The first dose should be given at birth, with intervals of at least 4 weeks between the remaining doses. If nOPV2 is added to the bOPV schedule, reduced immunogenicity for serotype 2 occurs.6Wilkinson AL Zaman K Hoque M et al.Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomised, controlled trial.Lancet Infect Dis. 2023; 23: 1062-1071Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar In the case of a polio outbreak, if infants have started their bOPV series, they might have reduced immunogenicity for serotype 2 with the addition of the modified nOPV2 dosing schedule within the bOPV schedule. Therefore, more data on the simultaneous administration of bOPV and nOPV2 is needed to ensure there is not a paradoxical immunogenic response to serotype 2 in the event of an outbreak. Vaccination campaigns with OPVs not only eradicated serotype 2, but they also resulted in decreased mortality rates among children aged between 1 day and 3 years.7Andersen A Fisker AB Nielsen S Rodrigues A Benn CS Aaby P National immunization campaigns with oral polio vaccine may reduce all-cause mortality: an analysis of 13 years of demographic surveillance data from an urban African area.Clin Infect Dis. 2021; 72: e596-e603Crossref PubMed Scopus (25) Google Scholar Reduction in mortality is attributed to decreased rates of respiratory infections from non-specific effects of OPVs.8Sørup S Stensballe LG Krause TG Aaby P Benn CS Ravn H Oral polio vaccination and hospital admissions with non-polio infections in Denmark: nationwide retrospective cohort study.Open Forum Infect Dis. 2015; 3ofv204PubMed Google Scholar, 9Bardenheier BH McNeil MM Wodi AP McNicholl JM DeStefano F Risk of nontargeted infectious disease hospitalizations among US children following inactivated and live vaccines, 2005-2014.Clin Infect Dis. 2017; 65: 729-737Crossref PubMed Scopus (39) Google Scholar The OPV confers cross protection against non-poliomyelitis enteroviruses, respiratory viruses, and herpes viruses due to early activation of CD4+ and CD8+ T cells via pattern-recognition receptors, reconfiguration of innate immune cells via epigenetic manipulation, and cross reaction between B cells and T cells, among other mechanisms.10Voroshilova MK Potential use of nonpathogenic enteroviruses for control of human disease.Prog Med Virol. 1989; 36: 191-202PubMed Google Scholar, 11Malave Sanchez M Saleeb P Kottilil S Mathur P Oral polio vaccine to protect against COVID-19: out of the box strategies?.Open Forum Infect Dis. 2021; 8ofab367Crossref PubMed Scopus (6) Google Scholar The intestinal and non-specific immunity conveyed by OPVs sustain herd immunity. Therefore, it is imperative to determine not only how a shortened nOPV2 dosing schedule affects intestinal and herd immunity to predict the risk for future polio outbreaks, but also how the modified schedule affects infant mortality overall. In conclusion, the paper by Mejia and colleagues provides promising findings in favor of a shorter nOPV2 vaccination schedule specifically for polio outbreak responses. We believe more studies with long-term follow-up are needed to determine whether a shorter vaccination schedule compromises the immune response to other routine vaccinations, including bOPV, or the intestinal and herd immunity of vulnerable populations. PM was a consultant for NKG Pharmaceuticals; received honoraria from the Med Learning Group and American Academy of HIV Medicine; and received conference fee support from Informed Horizons Education. SK reports receiving honoraria from Med Learning Group; serving on the Advisory Board for Gilead Sciences; and stock options in OrsoBio. Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican RepublicTwo nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2-week interval were non-inferior to those after the standard 4-week interval, but marked responses after a 1-week interval suggest that schedules with an over 1-week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine-derived poliovirus type 2 outbreaks. Full-Text PDF Open Access