Intestinal Immune Responses to Type 2 Oral Polio Vaccine (OPV) Challenge in Infants Previously Immunized With Bivalent OPV and Either High-Dose or Standard Inactivated Polio Vaccine

Elizabeth B Brickley, Carolyn B Strauch, Wendy F Wieland-Alter, Ruth I Connor, Shu Lin, Joshua A Weiner, Margaret E Ackerman, Minetaro Arita, M Steven Oberste, William C Weldon, Xavier Sáez-Llorens, Ananda S Bandyopadhyay, Peter F Wright, Elizabeth B Brickley, Carolyn B Strauch, Wendy F Wieland-Alter, Ruth I Connor, Shu Lin, Joshua A Weiner, Margaret E Ackerman, Minetaro Arita, M Steven Oberste, William C Weldon, Xavier Sáez-Llorens, Ananda S Bandyopadhyay, Peter F Wright

Abstract

Background: The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood.

Methods: In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2-specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants' intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples.

Results: Despite mIPV2HD's 4-fold higher type 2 polio D-antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants' intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2-specific IgA responses and stool neutralization were observed by 2 weeks after challenge.

Conclusions: Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge.

Clinical trials registration: NCT02111135.

Keywords: human challenge; inactivated vaccine; live oral vaccine; mucosal immunity; poliovirus.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Correlations between polio type 2–specific neutralization titers measured in serum at the time of challenge and monovalent type 2 oral polio vaccine (mOPV2) viral shedding (50% cell culture infective dose [CCID50]) (A), polio pseudovirus type 2–specific neutralization titers (B), and polio type 2–specific immunoglobulin A (IgA) levels (C), all measured in stool at 1 week after mOPV2 challenge (ie, 19 weeks of age). Black squares and bars indicate the median and interquartile ranges of the variables on the y-axes within each quintile of serum neutralization plotted against the mean serum neutralization within each quintile. Red markers indicate infants in the bivalent oral polio vaccine (bOPV)–bOPV-bOPV + trivalent inactivated polio vaccine (IPV) group (n = 47); gray markers indicate infants in the bOPV-bOPV-bOPV + monovalent high-dose type 2–specific IPV (mIPV2HD) group (n = 53). Circle-shaped markers indicate infants with any detectable viral shedding during postchallenge study visits (n = 79); X-shaped markers indicate infants with no detectable viral shedding during postchallenge study visits (n = 21).
Figure 2.
Figure 2.
Polio type 2–specific intestinal immune responses to monovalent type 2 oral polio vaccine (mOPV2) challenge in infants with any (n = 79) and no (n = 21) viral shedding detectable during postchallenge study visits: stool neutralization titers (A), immunoglobulin (Ig) A levels (B), IgA1 levels (C), and IgA2 levels (D), all measured in stool at 1–3 weeks after mOPV2 challenge (ie, 19–21 weeks of age). Data represent the combined responses of both vaccine groups. Scatter plots indicate individual measurements. LOESS curves (95% confidence interval) were fitted by shedding category. Abbreviations: Ig, immunoglobulin.
Figure 3.
Figure 3.
Correlations between levels of monovalent type 2 oral polio vaccine (mOPV2) viral shedding (50% cell culture infectious dose) and levels of polio type 2–specific mucosal antibodies and neutralization titers measured in stool collected at 1 week (A), 2 weeks (B), and 3 weeks (C) after mOPV2 challenge from infants with any viral shedding detectable during postchallenge study visits (n = 79). Spearman rank correlation coefficients were estimated from the combined responses of both vaccine groups. The narrowness of the ellipse and intensity of the color indicate the strength of a given correlation coefficient. The corresponding numerical values are defined by the vertical bar on the right. *P < .05; **P < .005. Abbreviations: CCID50, 50% cell culture infectious dose, Ig, immunoglobulin; Neutr., neutralization.

References

    1. Global Polio Eradication Initiative. Global eradication of wild poliovirus type 2 declared . Accessed 13 January 2017.
    1. World Health Organization. Global Polio Eradication Initiative annual report 2015. Geneva, Switzerland: WHO, 2016.
    1. World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva, Switzerland: WHO, 1988.
    1. Global Polio Eradication Initiative. Polio eradication and endgame strategic plan 2013–2018. Geneva, Switzerland: WHO, 2013.
    1. Kew OM, Sutter RW, de Gourville EM, Dowdle WR, Pallansch MA. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol 2005; 59:587–635.
    1. Global Polio Eradication Initiative. Polio this week as of 9 August 2017.
    1. Etsano A, Damisa E, Shuaib F et al. . Environmental isolation of circulating vaccine-derived poliovirus after interruption of wild poliovirus transmission—Nigeria, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:770–3.
    1. World Health Organization. Report of the SAGE Polio Working Group Meeting, 7–8 September 2015. Geneva, Switzerland: WHO, 2015.
    1. Centers for Disease Control and Prevention. Apparent global interruption of wild poliovirus type 2 transmission. MMWR Morb Mortal Wkly Rep 2001; 50:222–4.
    1. Grassly NC. Immunogenicity and effectiveness of routine immunization with 1 or 2 doses of inactivated poliovirus vaccine: systematic review and meta-analysis. J Infect Dis 2014; 210(Suppl 1):S439–46.
    1. Parker EP, Molodecky NA, Pons-Salort M, O’Reilly KM, Grassly NC. Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame. Expert Rev Vaccines 2015; 14:1113–23.
    1. Herremans TM, Reimerink JH, Buisman AM, Kimman TG, Koopmans MP. Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. J Immunol 1999; 162:5011–8.
    1. Herremans MM, van Loon AM, Reimerink JH et al. . Poliovirus-specific immunoglobulin A in persons vaccinated with inactivated poliovirus vaccine in the Netherlands. Clin Diagn Lab Immunol 1997; 4:499–503.
    1. Hird TR, Grassly NC. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge. PLoS Pathog 2012; 8:e1002599.
    1. O’Ryan M, Bandyopadhyay AS, Villena R et al. . Chilean IPV/bOPV Study Group. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study. Lancet Infect Dis 2015; 15:1273–82.
    1. Asturias EJ, Bandyopadhyay AS, Self S et al. . Latin American IPV001BMG Study Group. Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial. Lancet 2016; 388:158–69.
    1. Wright PF, Connor RI, Wieland-Alter WF et al. . Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants. Lancet Infect Dis 2016; 16:1377–84.
    1. Sáez-Llorens X, Clemens R, Leroux-Roels G et al. . Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial. Lancet Infect Dis 2016; 16:321–30.
    1. Wright PF, Wieland-Alter W, Ilyushina NA et al. . Intestinal immunity is a determinant of clearance of poliovirus after oral vaccination. J Infect Dis 2014; 209:1628–34.
    1. Arita M, Iwai M, Wakita T, Shimizu H. Development of a poliovirus neutralization test with poliovirus pseudovirus for measurement of neutralizing antibody titer in human serum. Clin Vaccine Immunol 2011; 18:1889–94.
    1. Weldon WC, Oberste MS, Pallansch MA. Standardized methods for detection of poliovirus antibodies. Methods Mol Biol 2016; 1387:145–76.
    1. Wei T, Sinko V. corrplot: visualization of a correlation matrix . Accessed 25 November 2017.
    1. Ogra PL, Karzon DT, Righthand F, MacGillivray M. Immunoglobulin response in serum and secretions after immunization with live and inactivated poliovaccine and natural infection. N Engl J Med 1968; 279:893–900.
    1. Onorato IM, Modlin JF, McBean AM, Thoms ML, Losonsky GA, Bernier RH. Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines. J Infect Dis 1991; 163:1–6.
    1. Cuba IPV Study Collaborative Group. Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba. N Engl J Med 2007; 356:1536–44.
    1. Herremans T, Kimman TG, Conyn-Van Spaendonck MA et al. . Immunoglobulin a as a serological marker for the (silent) circulation of poliovirus in an inactivated poliovirus-vaccinated population. Clin Infect Dis 2002; 34:1067–75.
    1. Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol 2011; 29:273–93.

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