This article is more than 5 years old. Information may no longer be current.
Space PCV7 doses at least eight weeks apart
Click Here to Manage Email Alerts
Primary doses of PCV7 should be spaced at least eight weeks apart when given in a two-dose priming (2+1) schedule, a study found.
Researchers in the United Kingdom studied 393 infants who received a priming dose of PCV7 (Prevnar, Wyeth) at 2 months of age, followed by a second priming dose either one month later (2-3 group) or two months later (2-4 group). All infants received a booster dose nine months after their first dose. Several other vaccines were issued concomitantly, including the meningococcal serogroup C vaccine (MCC Meningitec, Wyeth).
“The study was designed to determine whether an interval shorter than eight weeks may be satisfactory for PCV7 responses and/or MCC responses, thus providing more flexibility should a redesign of the immunization schedule become necessary,” the researchers wrote.
An earlier study by the same researchers proved the 2+1 dosing schedule, administered at 2 and 4 months of age followed by a booster, was as immunogenic as a three-dose priming schedule, leading the U.K. Department of Health to introduce PCV7 into the routine infant immunization schedule with only two priming doses. However, the researchers noted the earlier study examined a different, 9 valent PCV that was administered alongside vaccines that differed from those in the routine immunization schedule.
In the current study, an interim analysis revealed significantly higher IgG concentrations in the 2-4 group, leading researchers to halt the 2-3 group due to ethical concerns. The 2-3 group had significantly lower responses to serotypes 6B, 14 and 23F that persisted until one year of age. In contrast, MCC was equally immunogenic in both groups.
“This study has illustrated that within the accelerated infant immunization schedule in the United Kingdom, not all conjugate vaccines behave equally,” the researchers wrote. “Our study underlines how important it is to evaluate vaccines planned for use in national immunization programs together with concomitant vaccines that are to be used at the time of introduction.”
Overall, the priming doses of PCV7 performed significantly worse against 6B and 23F than PCV9 did in the researchers’ earlier study. However, after the booster dose of PCV7 responses were equivalent to titers achieved by a 3+1 schedule of PCV9.
“The evaluation of serotype 6B responses was particularly important in light of the information accruing on vaccine failures. At the time of writing, half of the 28 vaccine failures in the United Kingdom were caused by 6B infections,” the researchers wrote.
The researchers noted that the generic correlate of protection against all serotypes — considered an antibody concentration level of ≥0.35 µg/mL—is too high for some serotypes and too low for others. For example, two 23F failures were reported, whereas only 63% of infants achieved the protection threshold. And serotype 19F was indicated in 11 vaccine failures despite showing good immunogenicity (98% ≥0.35 µg/mL).
“When more serotype specific data accumulate from different surveillance systems around the world, the question of serotype specific correlate of protection needs to be revisited,” they wrote. – by Andy Moskowitz
Goldblatt D. Pediatr Infect Dis J. 2010;29:401-405.
Reduced dosing schedules for pneumococcal vaccine are attractive to decrease cost and also the number of vaccine doses required in the first year of life. However, fewer doses of pneumococcal conjugate might also provide reduced protection. In this study by Goldblatt and colleagues we see that the utility of reduced dose schedules also depends on when these doses are given. In this study, two doses at 2 and 3 months were not effective whereas two doses at 2 and 4 months provided antibody responses similar to a three dose schedule except for reduced levels of antibody for serotypes 6B and 23F. Interestingly the authors demonstrate that the conventionally accepted ELISA cut off of 0.35 ug/ml is not appropriate for all serotypes and that lower levels would seems indicated for 6B based upon OPA functional assay results. Since the pneumococcal conjugate vaccine is given in the UK with a booster dose in the second year of life and indirect population effects of the conjugate vaccine are strong, it is likely that the UK schedule employing two doses at 2 and 4 months with a booster in the second year of life will provide adequate protection in their population. Despite the fact that it has been more than ten years since the introduction of pneumococcal conjugate vaccine, we are still learning regarding appropriate dosing schedules and laboratory assessment of immunogenicity.
– Steven Black, MD
Infectious
Diseases in Children Editorial Board