Pneumococcal conjugate vaccine: are 3 doses equal to 4 doses?

After the introduction of routine infant immunization with 7-valent pneumococcal conjugate vaccine (PCV-7), the United States has witnessed a 74% decline in the number of children ,5 years of age diagnosed with invasive pneumococcal disease (IPD) and a 30% decline among all age groups. Likewise, rates of pneumoniaand otitis media-related medical visits among children, hospitalizations for pneumonia among children and young adults, and procedures for insertion of tympanostomy tubes also decreased. Because of increases in IPD owing to pneumococcal serotypes not included in the vaccine, 13-valent pneumococcal conjugate vaccine replaced PCV-7 10 years later. Although a major public health accomplishment, the current 4-dose 13-valent pneumococcal conjugate vaccine series administered at 2, 4, 6, and 12 to 15 months of age is now the most expensive vaccine series in the routinely recommended immunization schedule for persons 0 through 18 years of age. In this issue, Stoecker et al describe the cost savings if the United States adopted a reduced 3-dose pneumococcal conjugate vaccine (PCV) (21 1) schedule, as is recommended in many other countries. They suggest that possible increases in observed morbidity and mortality resulting from adoption of a reduced schedule could be mitigated by increasing vaccine coverage. Another option for a reduced schedule is 3 1 0; this regimen gives greater early protection but without the benefit of a booster dose (although the booster dose greatly enhances antibody response, there are no clinical differences documented to date). The 3 1 0 vaccine schedule is found in a few countries where vaccination after 9 months becomes less reliable. There have been 2 recent reviews of reduced immunization schedules for PCV. Both reviews note the variation by serotype in the immune response after the first 2 versus the first 3 doses. For most serotypes there are only modest reductions in the immune response after 2 doses; however, for serotypes 6B and 23F the diminution in immune responses is more significant. The World Health Organization estimated that an antibody concentration of 0.35 mg/mL for all PCVassociated serotypes correlates with clinical efficacy against IPDs related to that specific vaccine serotype. Although believed true for IPD, the antibody concentration correlating to protection from pneumonia or otitis media remains unknown. Interestingly, in a prelicensure immunogenicity study for PCV-7, responses to serotypes 6B and 23F did not achieve the 0.35 mg/mL concentration after 2 doses but did after 3, thus providing the rationale for the 4-dose series. These data further suggest that children receiving only 2 primary doses would remain vulnerable to infection owing to these serotypes and hence would need to rely on herd immunity for protection until receiving a boosting dose at 12 months of age. AUTHORS: Emmanuel B. Walter, MD, MPH and Dennis A. Clements, MD, PhD, MPH