A comparison of the immune response to two different oral polio vaccine regimes in Pakistan

An Emergency Action Plan for polio eradication in Pakistan in 2011 has recently been launched by the President of Pakistan which incorporates independent monitoring of immunization activities and increased political accountability at national, federal, district and union council levels, in the hope that eradication goals can be met quickly. As part of this effort, national EPI officers, WHO Polio Eradication Initiative, and other concerned partners are exploring ways of urgently suppressing polio virus activity in Pakistan. A proposed method to attain this is by conducting short-interval polio vaccination campaigns using type 1 monovalent oral polio vaccine (mOPV1) against the prevalent serotype (WPV1), particularly in areas with limited access due to security concerns. An earlier clinical trial in Egypt had demonstrated higher birth dose sero-conversion against WPV1, the main circulating global polio strain using mOPV1 compared to trivalent oral polio vaccine (tOPV) in 2006, leading many countries to use mOPV1 in subsequent supplemental immunization activities (SIA). A randomized, double-blinded trial in three centres in India has also established superiority of monovalent vaccines over trivalent and non inferiority of bivalent compared with monovalent OPV1 and OPV3. One of the major lessons learnt since Global Polio Eradication Initiative (GPEI) began, has been optimizing the impact of the new, highly immunogenic monovalent OPVs. This has proven difficult in practice, and in some settings has contributed to alternating outbreaks of the remaining wild poliovirus type 1 (WPV1) and wild poliovirus type 3 (WPV3) serotypes. The fast-tracked development and introduction of a bivalent OPV1&3 formulation in 2009, and its large-scale use in Supplemental Immunization Activities (SIAs) could complement the continued use of trivalent OPV in some SIAs and in routine immunization, as well as of monovalent OPVs in some mop-ups and SIAs where appropriate. Typically, SIA rounds are separated by an interval of ~30 days. It is possible that the same level of immunogenicity could be attained by shorter interval spacing as compared to the 30 day interval, allowing multiple SIA rounds to be conducted quickly to eradicate WPV circulation from an area in a very short time period of a few weeks instead of the current situation of having to conduct several rounds over a period of months and more children getting infected in areas of high WPV transmission. For example, in Pakistan, in 2010, intervals between SNIDs ranged from 5-9 weeks. Shorter interval SIA rounds would also have the added benefit of allowing multiple "sweep throughs" in areas of high transmission in a short period of time, increasing the chance that children missed on a previous round will get vaccinated in subsequent rounds. However, there is limited knowledge on the effect of shorter intervals of mOPV vaccination on immunogenicity levels in young children and comparative efficacy of mOPV1 versus bivalent oral polio vaccine containing serotypes 1 and 3 (bOPV1&3). It is assumed more vaccinations administered within a shorter period of time would be non-inferior to regular intervals, defined as an immunization round every 30 days. Although shorter interval immunization rounds were carried out in Somalia, Afghanistan, and Kenya, and were successful in eradicating polio from these areas, there was no documentation of immunogenicity levels in these children. In order to generate data on 2-dose seroconversion with short interval monovalent OPV1 administration, and standard interval monovalent OPV1 and bivalent OPV (1&3) administration, we propose to assess additional programmatic options for short-interval SIA rounds in Pakistan and conduct a clinical trial in Karachi, Pakistan where immunogenicity of supplemental mOPV doses in a naive population (newborns) needs objective evaluation.