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correspondence

Indian Pediatr 2012;49: 423-424

Reply


Vipin M Vashishtha

Convener, IAP Committee on Immunization, Mangla Hospital & Research Center, Shakti Chowk,
Bijnor 246 701, UP, India.
Email: [email protected] ,[email protected]


The current IAP recommendations state, "IPV may be offered as catch up vaccination for children less than 5 years of age who have completed primary immunization with OPV. IPV can be given two doses at 2 month interval" [1]. The primary immunization with OPV implies here three doses of OPV at 6, 10, and 14 weeks.

Coming to his specific query on ‘priming’ by OPV, one should know that live vaccines do not work on the "prime-boost" principle. It is the property of killed vaccines, especially the ‘T-cell dependent’ protein, conjugate vaccines that induce memory B-cell formations in lymphoid tissues. These memory B cells convert to high-affinity antibodies secreting plasma cells on re-exposure to specific antigen (or to the next dose of the same vaccine). Hence, immunologically, priming means formation of memory B cells or in other term, the ‘boostability’ of an immune response induced by an antigen/vaccine.    

When OPV is given by mouth, the vaccine viruses reach the intestines where they must establish infection (vaccine virus "take") before an immune response may occur. Infection may or may not occur each time a dose is given  by mouth, therefore multiple  attempts are necessary to ensure the  ’take’ of each type at least once. In this respect OPV differs from other live virus vaccines which require only one dose for immunizing susceptible subjects [2].  

When OPV is given to a child, three possible actions can be anticipated- one, the child may fully seroconvert to all three types of viruses with elicitation of all types of immune responses; second, the dose fails to elicit any serological response and the child may still remain immunologically ‘naive’, and third, the dose elicits only partial immune responses which may or may not include formation of memory B cells. Hence, a single dose of OPV may seroconvert, prime or fail to have any impact on an individual vaccine. Administration of an OPV dose at birth (zero dose) serves as a ‘priming dose’ since it is not protective to the vaccine (i.e. it fails to induce protective levels of neutralizing antibodies owing to interfering maternal antibodies and secretary IgA in breast milk) but still manage to produce enough memory B cells that can be boosted to have improved serologic responses to future doses. To document whether a dose has indeed primed an individual or not, one needs to show the presence of memory B cells by eliciting an anamenstic immune response to next vaccine dose.

Immune responses to OPV are quite unpredictable and erratic, especially in tropical countries like India. For reasons that are not yet clear, the vaccine virus take rate is lower in developing countries than in North America or Europe. In industrialized countries, after complete primary vaccination with three doses of OPV, 95% or more of recipients seroconvert and develop long-lasting immunity to all three poliovirus serotypes [3]. In a trial in the United States, 39% of vaccinees seroconverted to poliovirus type 1, 84% to poliovirus type 2 and 71% to poliovirus type 3 after a single dose of OPV. After receipt of two doses of OPV, seroprevalence was 92% to poliovirus type 1, 100% to poliovirus type 2 and 96% to poliovirus type 3; and after three doses of OPV, 97% had antibodies to poliovirus type 1, 100% to poliovirus type 2 and 100% to poliovirus type 3 [3].

However, OPV appears to be considerably less immunogenic in developing countries. A comprehensive review of the immunogenicity of OPV in developing countries reported that a weighted average of only 73%,  90% , and 70% of children participating in these studies have detectable antibody to poliovirus types 1, 2 and 3, respectively, after three OPV doses [3].  Data from India suggest that seroconversion rates after three doses of OPV average 65%, 96% and 63% for Types I, II and III, respectively. Sero-conversion Index (arithmetic mean of seroresponses to all three types of polioviruses) to OPV in children in Vellore was noted as 37 after 1 dose; 54 after 2 doses; 78 after 3 doses, and 87 after 5 doses [2, 4].

Hence, it is very difficult to tell how many doses will ‘prime’ a vaccinee. This is difficult to predict in developing countries but in industrialized countries it can be predicted with much more certainty. If we go by the above studies, it can be assumed that in industrialized countries, three doses of OPV not only prime but also seroconvert 95% of individuals, however, in India the same proportion would be only 78%. And if the most recent estimates from UP are taken in to account, this would come to a mere 39%!

There are reports to suggest that even one dose of IPV following multiple doses of OPV in a tropical setting helps to narrow the humoral immunity gaps to all three polio virus serotypes [5]. Similarly, mucosal immunity is also boosted following one or two doses of IPV after history of multiple doses of OPV. This is the reason why IAPCOI has recommended only two doses of IPV to OPV primed children.

References

1. Polio vaccines. In: Yewale V, Choudhury P, Thacker N, Editors. IAP Guide Book on Immunization. 6th eds. Mumbai: IAP;2011. p.53-60.

2. John TJ. Immunization against polioviruses in developing countries. Rev Med Virol. 1993;3:149-60.

3. Sutter RW, Kew OM, Cochi SL. Poliovirus vaccine - live. In: Plotkin SA, Orenstein WA, Offit PA (Ed) Vaccines. 5th Edition. Saunders Elsevier; 2008. p. 631-85.  

4. John TJ. Antibody response of infants in tropics to five doses of oral polio vaccine. Br Med J. 1976;1:812.

5. Polio Eradication Committee; Indian Academy of Pediatrics, Vashishtha VM, Kalra A, John TJ, Thacker N, Agarwal RK. Recommendations of 2nd National Consultative Meeting of Indian Academy of Pediatrics (IAP) on polio eradication and improvement of routine immunization. Indian Pediatr. 2008;45:367-78.

 

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