Mucosal immunity to poliovirus

Abstract

A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed to prevent the development of paralytic disease and interrupt transmission of the virus. Central to these efforts is the goal of inducing mucosal immunity able to limit virus replication in the intestine. Recent clinical trials have evaluated new combined regimens of poliovirus vaccines, and demonstrated clear differences in their ability to restrict virus shedding in stool after oral challenge with live virus. Analyses of mucosal immunity accompanying these trials support a critical role for enteric neutralizing IgA in limiting the magnitude and duration of virus shedding. This review summarizes key findings in vaccine-induced intestinal immunity to poliovirus in infants, older children, and adults. The impact of immunization on development and maintenance of protective immunity to poliovirus and the implications for global eradication are discussed.

Fig. 1. Global clinical trials of poliovirus vaccines in infants, children and adults.

Clinical trials were conducted to assess induction of polio type-specific immunity in response to immunization and OPV challenge in infants (FIDEC, Chile, Panama)^–, children (Lithuania), and adults (Sweden, Belgium)^,. Induction of polio type-specific intestinal immunity for each trial was evaluated in a related set of studies^–,,,. Details of the primary immunization schedules and type-specific OPV challenges for each study are published and briefly summarized here. FIDEC (Fighting Infectious Diseases in Emerging Countries): Infants were randomized to receive a primary series of tOPV-tOPV-tOPV, bOPV-bOPV-bOPV or bOPV-bOPV-bOPV+IPV at 6, 10, and 14 weeks of age, followed by mOPV2 challenge at 18 weeks. Chile: Infants were randomized to receive IPV-IPV-IPV, IPV-IPV-bOPV, or IPV-bOPV-bOPV at 8, 16, and 24 weeks of age, followed by mOPV2 challenge at 28 weeks. Panama: Infants received bOPV at 6, 10, and 14 weeks of age and were randomized to receive a standard dose of IPV or a monovalent high-dose type 2-specific IPV (mIPV2HD) at 14 weeks, followed by mOPV2 at 18 weeks. Lithuania: Children (ages 1–5 years) who had received 3–4 doses of IPV at 2, 4, 6, and 18 months of age were challenged with a dose of mOPV2 at study entry. A second dose of mOPV2 was given 28 days after the first in a subset of the children. Sweden: Adults who had received 3–4 doses of IPV in childhood were challenged at study entry with mOPV1. Belgium: Adults who had received up to six doses of IPV in childhood were challenged with a single dose of nOPV2 at study entry.

Fig. 2. Age-related decline in intestinal neutralizing antibody responses to poliovirus following challenge with OPV.

Polio type-specific neutralizing responses were measured in stool following OPV challenge in a series of studies of infants, children, and adults participating in clinical trials of poliovirus vaccines^–,,,. Data represent the reverse cumulative distribution of polio type-specific neutralizing titers measured in stool 2 weeks after OPV challenge in each study. The magnitude of the enteric response is shown as the cumulative probability of participants achieving a neutralization titer within the specified range. Comparative responses are shown for infants challenged with mOPV2 at 18–28 weeks (A–C); children challenged with mOPV2 at 1–5 years (D) and adults challenged with mOPV1 (E) or nOPV2 (F) at 18–50 years. Polio type-specific stool neutralization titers were measured as described^–,,, and all samples were tested in the same laboratory using a standardized neutralization assay. Data for each study was analyzed independently to generate reverse cumulative distribution curves. FIDEC, Fighting Infectious Diseases in Emerging Countries.