Pneumococcal Conjugate Vaccine (PCV) Schedules for the Northern Territory (NT): Randomised Controlled Trial of Booster Vaccines to Broaden and Strengthen Protection From Invasive and Mucosal Infections.

BACKGROUND:

PCV13 is now the recommended PCV in Australia, as 3+0 for non-Indigenous children and as 3+1 for Indigenous children in Western Australia, Queensland and Northern Territory. The decision to recommend PCV13 over PHiD-CV10 has been primarily driven by the increase in cases of invasive pneumococcal disease due to serotype 19A(1). However for the NT, in the last 3 years there has been one case of serotype 3, 6A or 19A invasive pneumococcal disease (IPD) per year in Indigenous children less than 2 years of age. By contrast, almost 20% of young Indigenous children have perforated tympanic membranes of which 60% are associated with NTHi, compared to 3% having serotypes 3, 6A or 19A.

The PREV-IX_COMBO trial is a randomised controlled trial (RCT) of these two pneumococcal conjugate vaccines currently licensed in Australia. Participating Indigenous infants living in remote communities in 4 regions of the NT are randomised between 28 and 38 days of age and allocated to one of three groups: PHiD-CV10 at 2, 4, 6 months or PCV13 at 2,4,6 months, or an investigational group of a 4-dose combination schedule of PHiD-CV10 at 1,2, and 4 months plus PCV13 at 6 months.

PREV-IX_BOOST builds on PREV-IX_COMBO to address questions not answerable by a booster trial in the general population:

The 7 month visit is the final assessment included in the PREV-IX_COMBO trial. In October 2011 the standard PCV schedule for all Indigenous babies in the NT switched from PHiD-CV10 to PCV13 at 2, 4, 6 and 18 months of age. Thus, all babies in PREV-IX_COMBO will go on to receive PCV13 at 18 months of age as a part of standard care. An alternative and innovative option is to take this opportunity to answer these questions: should PCV13 or PHiD-CV10 vaccine be the booster vaccine for infants in the three PREV-IX_COMBO groups, and at what age should the booster be given? Secondary questions: By randomising the three different primary course groups to booster dose of either PHiD-CV10 or PCV13, a number of secondary questions can be proposed. Outputs include the comparative benefit (immune and carriage correlates) of schedules such as 3+1 PCV13, 3+1 PHiD-CV10, and mixed vaccine schedules such as single dose PCV13 or single dose PHiD-CV10 boosters following alternate vaccines in the primary course, and booster options following the early and mixed 4-dose primary course. Furthermore the design will allow for an evaluation at 18 months of age, of a 12 month boost versus no boost of specific vaccine components unique to each of these vaccines. For example, a comparison of the booster effect of HiD (in PHiD-CV10) with no HiD boost (PCV13) on antibody concentration and nasopharyngeal carriage at 18 months. By combining some of these groups it will be possible to compare more subtle differences such as differences in immunogenicity of serotypes shared by the two vaccines (1,4,5,6B,7F,9V,14,18C,19F,23F) but with different carrier proteins and thus anticipated differences in immunogenicity.