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

Abstract

These results from a 2014 phase 2 clinical trial in Panamanian infants suggest that high-dose inactivated polio vaccines (IPVs), like standard IPVs, are largely ineffective at inducing levels of intestinal immune responses requisite to control poliovirus shedding.

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden

“…Similarly, in a 2010 Omani clinical trial in which infants were vaccinated with IPV at 2, 4 and 6 months and then challenged with mOPV1 at 7 months, 73% of the infants had undetectable (ie, <2) poliovirus type 1-specific stool neutralising titers following the primary IPV vaccine series,15 while 63% went on to shed vaccine virus on challenge 30. Analogous failures to induce poliovirus type 2-specific mucosal immunity by IPV have been observed as part of trials in Panama11 and Chile12 among infants who were vaccinated with three doses of IPV before challenge with mOPV2. Furthermore, in a faecal monitoring study conducted in response to the 2013 silent outbreak of wild poliovirus type 1 in Israel, 85% of faecal samples that were positive for virus were collected from children (<10 years of age) who had been previously vaccinated with at least three doses of IPV 31…”

“…The observation that, despite documented viral replication and sustained excretion, the Swedish study participants failed to mount an intestinal antibody response to mOPV1 challenge was unanticipated and in marked contrast to the experiences of five OPV challenge studies in paediatric participants 10–12 15 29. For both of the aforementioned mOPV1 challenge studies in the USA29 and Oman,15 rises in poliovirus type 1-specific intestinal immune markers (ie, IgA in stool specimens and neutralising activity, respectively) were reported in the IPV recipients following mOPV1 receipt.…”

“…Stool samples collected from the study participants and stored frozen at the National Institute for Public Health and the Environment (Bilthoven, The Netherlands) were identified, thawed, aliquoted and refrozen prior to shipping to the USA 10 11 15 25. This excluded any possibility of chloroform treatment, which is used in virus titration but has been previously shown to inactivate antibody activity (Wright laboratory, unpublished data).…”

“…Today, >50 years of scientific research confirm that live-attenuated oral polio vaccines (OPVs) administered in childhood are capable of stimulating the production of poliovirus-specific neutralising antibodies in nasopharyngeal and gastrointestinal mucosal tissues9–12 and thereby inhibiting poliovirus replication on subsequent homologous OPV challenge 13–15. In contrast, current evidence suggests childhood immunisation schedules based exclusively on inactivated (killed) polio vaccines (IPVs) induce only negligible intestinal immunity3 9 11 16 and fail to interrupt viral replication on subsequent exposure to either vaccine virus14 17 18 or circulating wild-type viruses 19–21…”

“…Several studies have suggested that paediatric OPV schedules (ie, OPV-first schedules) may educate the intestinal immune system such that a supplemental late dose of IPV may significantly boost children’s preexisting mucosal neutralising activity 5 22 23. On the other hand, a series of recent trials in Latin American infants have demonstrated that children who instead received primary vaccine series with IPV (ie, IPV-first schedules) shed high quantities of vaccine virus after receiving a supplemental challenge dose of OPV,17 18 but consistently developed strong poliovirus type-specific enteric neutralising activity by 2 weeks’ post-OPV challenge 11 12…”