Priming after a Fractional Dose of Inactivated Poliovirus Vaccine

Pedro Kouri Institute, Havana, Cuba.
New England Journal of Medicine (Impact Factor: 55.87). 01/2013; 368(5):416-24. DOI: 10.1056/NEJMoa1202541
Source: PubMed


To reduce the costs of maintaining a poliovirus immunization base in low-income areas, we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine (IPV).
We compared the immunogenicity and reactogenicity of a fractional dose of IPV (one fifth of a full dose) administered intradermally with a full dose administered intramuscularly in Cuban infants at the ages of 4 and 8 months. Blood was collected from infants at the ages of 4 months, 8 months, 8 months 7 days, and 8 months 30 days to assess single-dose seroconversion, single-dose priming of immune responses, and two-dose seroconversion. Specimens were tested with a neutralization assay.
A total of 320 infants underwent randomization, and 310 infants (96.9%) fulfilled the study requirements. In the group receiving the first fractional dose of IPV, seroconversion to poliovirus types 1, 2, and 3 occurred in 16.6%, 47.1%, and 14.7% of participants, respectively, as compared with 46.6%, 62.8%, and 32.0% in the group receiving the first full dose of IPV (P<0.008 for all comparisons). A priming immune response to poliovirus types 1, 2, and 3 occurred in 90.8%, 94.0%, and 89.6% of participants, respectively, in the group receiving the fractional dose as compared with 97.6%, 98.3%, and 98.1% in the group receiving the full dose (P=0.01 for the comparison with type 3). After the administration of the second dose of IPV in the group receiving fractional doses, cumulative two-dose seroconversion to poliovirus types 1, 2, and 3 occurred in 93.6%, 98.1%, and 93.0% of participants, respectively, as compared with 100.0%, 100.0%, and 99.4% in the group receiving the full dose (P<0.006 for the comparisons of types 1 and 3). The group receiving intradermal injections had the greatest number of adverse events, most of which were minor in intensity and none of which had serious consequences.
This evaluation shows that vaccinating infants with a single fractional dose of IPV can induce priming and seroconversion in more than 90% of immunized infants. (Funded by the World Health Organization and the Pan American Health Organization; Australian New Zealand Clinical Trials Registry number, ACTRN12610001046099.).

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Available from: Sonia Resik, Jul 24, 2014
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    • "The Polio Eradication and Endgame Strategic Plan 2013–2018 recommends that one dose of Inactivated Poliovirus Vaccine (IPV) is added to the routine immunization programs in all countries that currently use only OPV by the end of 2015 [15]. IPV has been successfully used in many polio-free countries to maintain population protection against polioviruses, and it has been demonstrated that IPV induces humoral immunity in naive children and boosts mucosal immunity in those who had previously received OPV [16] [17] [18]. IPV together with OPV has recently been used in SIAs to control outbreaks (Kenya) or to accelerate poliovirus eradication in persistent endemic areas (Nigeria) [19]. "
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    ABSTRACT: 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. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Vaccine
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    • "Unlike orally administered OPV, IPV needs to be injected. Data suggests that one dose of IPV will provide serological protection through priming or seroconversion to approximately 90% of naïve infants [6], and establish an immunity base for poliovirus type 2, that can be rapidly boosted in a threatening outbreak scenario. In addition to mitigating the risk of paralysis caused by vaccine-derived poliovirus type 2 (VDPV2), IPV also boosts mucosal immunity in previously OPV-vaccinated recipients [7]. "
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    ABSTRACT: The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV.Methods Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination).ResultsComplete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified.InterpretationOne of the two new injector demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan.
    Full-text · Article · Nov 2014 · Vaccine
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    • "A key element of the endgame is the removal of the type 2 component of the oral poliovirus vaccine, facilitated by the introduction of an affordable inactivated injectable polio vaccine (IPV) globally. A study conducted in Cuba reported a breakthrough in the search for an 'affordable IPV' with one fifth dose of IPV found to achieve 63% seroconversion, and 99% priming against poliovirus type 2 [1]. This result was crucial to a landmark SAGE recommendation that all countries should introduce at least one dose of IPV into their routine immunization programmes to mitigate the risks associated with withdrawal of OPV2. "
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    ABSTRACT: The Developing Countries Vaccine Manufacturers’ Network (DCVMN) brought together nearly 220 senior representatives of governmental and non-governmental global health organizations, as well as corporate executives of emerging vaccine manufacturers, from 26 countries for a two-day tailored lectures, Q&A sessions, CEOs panel discussion and networking opportunities, followed by a vaccine-technology symposium and visit to manufacturing facilities in Hanoi, Vietnam. Participants included representatives of 38 vaccine manufacturers, as well as international partners and collaborating research institutions, with 39% female participants. The Vice-Minister of Health to Vietnam commended the speakers and participants to this Annual General Meeting, devoted to achieve our common goal of protecting people against infectious diseases with better vaccines, for a healthier life. He reminded the audience that the first vaccine produced in Vietnam was oral polio vaccine (OPV) in the early 1960s and contributed to polio eradication in Vietnam, in 2000. Through its manufacturing resources, Vietnam eliminated neonatal tetanus in 2005, and has controlled measles and hepatitis B spread. The Ministry of Health hopes that by sharing experiences, delegates at this conference will foster international cooperation and partnerships among organizations. CEOs elaborated on challenges and opportunities for emerging countries.
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