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.