SummaryThe WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high‐cost, limited supply of IPV, persistent circulating vaccine‐derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low‐cost cold chain‐free plant‐made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50‐fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant‐derived adjuvants after single priming with IPV significantly increased VP1‐IgG1 and VP1‐IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (~3.17–10.17 log2 titre) and seropositivity (70–90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant‐cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA‐approved antigens and adjuvants are discussed.

Background: Acute flaccid myelitis (AFM), a serious paralytic illness, was first recognized as a distinct condition in 2014, when cases were reported concurrent with a large U.S. outbreak of severe respiratory illness caused by enterovirus D-68 (EV-D68). Since 2014, nationwide outbreaks of AFM have occurred every 2 years in the United States; the cause for the recent change in the epidemiology of AFM in the United States, including the occurrence of outbreaks and a biennial periodicity since 2014, is under investigation. This report updates clinical, laboratory, and outcome data for cases reported to CDC during 2018.Methods: Clinical data and specimens from persons in the United States who met the clinical criterion for AFM (acute onset of flaccid limb weakness) with onset in 2018 were submitted to CDC for classification of the illnesses as confirmed, probable, or non-AFM cases. Enterovirus/rhinovirus (EV/RV) testing was performed on available specimens from persons meeting the clinical criterion. Descriptive analyses, laboratory results, and indicators of early recognition and reporting are summarized.Results: From January through December 2018, among 374 reported cases of AFM, 233 (62%) (from 41 states) were classified as confirmed, 26 (7%) as probable, and 115 (31%) as non-AFM cases. Median ages of patients with confirmed, probable, and non-AFM cases were 5.3, 2.9, and 8.8 years, respectively. Laboratory testing identified multiple EV/RV types, primarily in respiratory and stool specimens, in 44% of confirmed cases. Among confirmed cases, the interval from onset of limb weakness until specimen collection ranged from 2 to 7 days, depending on specimen type. Interval from onset of limb weakness until reporting to CDC during 2018 ranged from 18 to 36 days, with confirmed and probable cases reported earlier than non-AFM cases. Conclusion:Identification of risk factors leading to outbreaks of AFM remains a public health priority. Prompt recognition of signs and symptoms, early specimen collection, and complete and rapid reporting will expedite public health investigations and research studies to elucidate the recent epidemiology of AFM and subsequently inform treatment and prevention recommendations.Please note: An erratum has been published for this issue. To view the erratum, please click here.

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Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9–12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV + IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n = 386), 73.6% (n = 332), and 70.7% (n = 319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n = 448), 87.0% (n = 441) and 83.6% (n = 397) in the normally nourished group (p < 0.05). Children had previously received 9–10 doses of bOPV (80%) or tOPV (20%). One dose of IPV + bOPV given to malnourished children increased their serological protection (PV1, n = 201, 97.6%; PV2, n = 198, 96.1% and PV3, n = 189, 91.7%) to parity with normally nourished children who had not received IPV (p = <0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV + bOPV than in those with bOPV only (p < 0.001) in both strata. Shedding of polioviruses in stool did not differ between study groups and ranged from 2.4% (n = 5) to 7.1% (n = 15). In malnourished children the shedding was reduced after bOPV + IPV compared to bOPV only.Chronically malnourished infants were more likely to be unprotected against polioviruses than normal infants. bOPV + IPV helped close the immunity gap better than bOPV alone.

Gestational enterovirus (EV) infections have been associated with an increased risk for type 1 diabetes in the offspring. We therefore analyzed non-diabetic mothers for EV exposure in early pregnancy in relation to type 1 diabetes HLA-DQ risk genotypes and seroconversion to islet autoantibodies during pregnancy. Non-diabetic mothers who had islet autoantibodies (n = 365) against glutamic acid decarboxylase (GADA), islet antigen-2 autoantibodies (IA-2A), or insulin autoantibodies (IAA), in early pregnancy and at delivery were compared to islet autoantibody-negative mothers (n = 1457) matched for age and sampling date. Mothers were genotyped for HLA-DQ and analyzed for both EV-RNA and EV-IgM. EV-IgM, but not EV-RNA, was detected during early pregnancy in 12% of islet autoantibody-positive mothers compared to 11% of the controls. In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed an increased risk for islet autoantibodies at delivery (OR 1.85; p = 0.001). After adjusting for parity, maternal age, year of birth, and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for islet autoantibodies (OR 3.10; 95% CI 1; p = 0.008). EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers with HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes.

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The immunization program in Sri Lanka consistently reaches >90% coverage with oral poliovirus vaccines (OPV), and no polio supplementary vaccination campaigns have been conducted since 2003. We evaluated serological protection against polioviruses in children. A cross-sectional community-based survey was performed in three districts of Sri Lanka (Colombo, Badulla, and Killinochi). Randomly selected children in four age groups (9-11 months, 3-4 years, 7-9 years, and 15 years) were tested for poliovirus neutralizing antibodies. All 400 enrolled children completed the study. The proportion of seropositive children for poliovirus Type 1 and Type 2 was >95% for all age groups; for poliovirus Type 3 it was 95%, 90%, 77%, and 75% in the respective age groups. The vaccination coverage in our sample based on vaccination cards or parental recall was >90% in all age groups. Most Sri Lankan children are serologically protected against polioviruses through routine immunization only. This seroprevalence survey provided baseline data prior to the anticipated addition of inactivated poliovirus vaccine (IPV) into the Sri Lankan immunization program and the switch from trivalent OPV (tOPV) to bivalent OPV (bOPV).

Summary Background Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. Methods This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2.5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1–1 week), 2 weeks (mOPV1–2 weeks), or 4 weeks (mOPV1–4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV–4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants’ families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Findings Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72.4–86.1) with mOPV1–1 week, 108/135 (80%, 73.2–86.8) with mOPV1–2 weeks, 129/148 (87%, 80.9–92.0) with mOPV1–4 weeks, and 107/136 (79%, 71.8–85.6) with bOPV–4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. Interpretation We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict—eg, during cease-fire periods. In s...