Evaluation of PCV Schedules in a Naive Population in Vietnam

Background Pneumococcal conjugate vaccine (PCVs) have substantially reduced the burden of pneumococcal disease. WHO currently recommends giving PCVs as 3 doses - either 3 doses in infancy with Pentavalent vaccine (3p+0), or two doses in infancy followed by a booster around the end of the first year of life (2p+1). The 3p+0 schedule is used in many countries introducing PCV with Gavi support while several European countries are using 2p+1 schedule. However, their high price and the current recommendation for at least 3 doses to achieve full individual protection for infants, introduces a substantial financial burden. As a result, many middle income countries have not yet introduced PCVs, and low income countries that have introduced PCVs with the aid of the Gavi, the Vaccine Alliance, may not be able to sustain PCV vaccination after graduating from GAVI support.

To date PCV programs have been designed to provide optimal individual protection of the vaccinees, yet experience in developed countries indicates that herd immunity, which is generated by reducing carriage and hence transmission of vaccine serotypes in the community, controls vaccine type pneumococcal disease in vaccinated and unvaccinated individuals alike [1]. Using PCV impact on vaccine type carriage as a marker of vaccine type disease [2], the investigators will investigate the feasibility of reducing the number of infant doses in the PCV immunization schedule, to make more efficient use of herd immunity in the protection against pneumococcal disease.

Study aim and objectives Primary objective 1- The investigators will measure the effect of the 1p+1 schedule on vaccine type pneumococcal carriage and non-inferiority compared to a 2p+1 or 3p+0 schedule in (a) children aged 4-11 months, i.e. after the age of a completed primary series and before the age where they would receive a booster dose (this is the population that is most at risk for pneumococcal disease and is likely to receive less direct protection from a reduced primary series), and (b) children aged 14-24 months, i.e. after the age where a booster dose is given in the treatment arms(this is the beginning of the age period when most intense transmission of pneumococci is believed to occur).

Secondary objective 1 - The investigators will measure the effect (both direct + indirect effects) of the 0p+1 schedule against vaccine type carriage and non-inferiority against a 2p+1 or/and 3p+0 schedules respectively in (a) children aged 4-11 months, and (b) children aged 14-24 months,.

Secondary objective 2 - The investigators will measure the effect of the 1p+1 and 0p+1 schedules against vaccine type carriage and non-inferiority against a 2p+1 or 3p+0 schedules respectively among unvaccinated mothers.