Where are the immunity gaps?

A number of studies looking at the immunity profile of infants and children in India have now been completed and preliminary results are available. These studies include:

1. re-testing of the 2007 seroprevalence survey in Mordadabad district in Uttar Pradesh state
2. the 2009 Moradabad trial; and,
3. the seroprevalence survey among cases with acute flaccid paralysis (AFP) in western Uttar Pradesh.

The laboratory processing of these samples was conducted by the Enterovirus Research Centre in Mumbai, India and by the US Centers for Disease Control and Prevention (CDC) in Atlanta, USA. While the detailed analyses are pending finalization and the ensuing results will likely be published in the scientific literature in the course of 2010, there are a number of interesting and sometimes unexpected preliminary results that will influence programmatic action and the research agenda for 2010–2011. These include:

1. the 2009 Moradabad trial reporting >99% seroprevalence to poliovirus type 1 among 6–9 months old infants;
2. significant improvements in type 1 seroprevalence between the 2007 survey and the 2009 trial in infants aged 6-9 months (approximately 20% points) due to substantial increases in the number of polio vaccine doses received;
3. the substantially lower levels of seroprevalence for types 2 and 3 in all three studies; and,
4. the ability of one dose of inactivated polio vaccine (IPV) to close the immunity gaps very effectively, with 100% for type 2 and >90% for type 1 (it is important to note that during this particular investigation, a fractional-dose of IPV delivered intradermally did not perform as effectively as a whole-dose IPV, though further research to establish a potential role of fractional-dose IPV is needed). This immunity gap closure was observed already in the seven-day blood sample.

It appears that even in the most difficult areas in northern India, the polio eradication programme can achieve very high humoral immunity levels (>99%) to type 1, somewhat at the cost of lower levels for types 2 and 3, respectively. The recently developed bivalent OPV (containing types 1 and 3) should help to alleviate this issue. The AFP study also demonstrated lower type 2 and 3 seroprevalence levels in <5 year-old children, questioning the postulated “high” force-of-infection of these viruses in northern India. And finally, the observation that 90%–100% of seronegative infants seroconvert seven days after receipt of an IPV dose, suggests that most of these infants had been primed and respond with an anamnestic immune response.

In summary, the existing immunity gaps in northern India are now focused primarily for types 2 and 3. As noted above, these studies raise a number of important issues: it is apparent that more research is needed both to characterize these immune responses, especially for mucosal immunity, and to devise new means to measure mucosal immunity and institute new measures to boost mucosal immunity. To that end, a number of studies are being planned for implementation in India and Cuba in 2010.