Reassessing the 1 + 1 pneumococcal conjugate vaccine schedule

The primary endpoint selected by David Goldblatt and colleagues,1Goldblatt D Southern J Andrews NJ et al.Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial.Lancet Infect Dis. 2018; 18: 171-179Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar which was used to support a pneumococcal conjugate vaccine (PCV) programme consisting of one primary dose and one booster dose (1 + 1), is a poor indicator of protection during the first year of life, and contrary to O'Brien's Comment,2O'Brien KL When less is more: how many doses of PCV are enough?.Lancet Infect Dis. 2018; 18: 127-128Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar this programme is not likely to be feasible for implementation in countries supported by Gavi, the Vaccine Alliance. Results from an immunogenicity test at 13 months are not appropriate to assess the 1 + 1 programme. This timepoint primarily measures the effect of the booster dose, but does not differentiate between a two-dose and a one-dose primary series. Significant reductions in immunogenicity for the one-dose group observed at 5 months are brushed off as “expected”, but these results are more relevant than the results at 13 months when comparing the two schemata. Protection during the first year of life is vital, given the burden of disease: 50% of pneumococcal meningitis and 65% of pneumococcal pneumonia cases occur in this vulnerable age group. 3Russell F Sanderson C Temple B Mulholland K Global review of the distribution of pneumococcal disease by age and region. World Health Organization, Geneva2011http://www.who.int/immunization/sage/6_Russel_review_age_specific_epidemiology_PCV_schedules_session_nov11.pdfGoogle Scholar Goldblatt and colleagues1Goldblatt D Southern J Andrews NJ et al.Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial.Lancet Infect Dis. 2018; 18: 171-179Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar state that this 1 + 1 programme should only be enacted in settings in which “PCV coverage, particularly for the booster dose, is high at local, regional, and national level, PCV has been used for some years, and pneumococcal disease and carriage of vaccine serotypes has already been controlled in all age groups”, and O'Brien further requires a system with no “fluctuations in coverage or delays in dosing”. Even with these conditions in place, the 1 + 1 programme still fails to anticipate the arrival of third-generation PCVs, which will alter coverage, carriage, and control. Despite the aforementioned qualifiers, the Joint Committee of Vaccination and Immunisation used data from this trial to justify implementation of a 1 + 1 PCV programme for infants in the UK, even though second-generation vaccine serotypes still account for the majority of invasive pneumococcal disease in adults (49% of cases were serotype 3, and 29% were serotype 19A).4Joint Committee on Vaccination and ImmunisationMinutes of the meeting on 04 October 2017.https://www.jostrust.org.uk/sites/default/files/minute_2017_10_draft.pdfGoogle Scholar The allure of potential cost savings has prevailed over all caveats. Now that the UK has implemented it, other countries may be tempted to adopt a 1 + 1 programme as well, particularly with O'Brien's Comment describing savings of “roughly $1·5 billion […] over a 10-year time period” for Gavi eligible countries, for which the likelihood of meeting the conditions necessary for the success of this programme is far lower than for the UK. The cost of pneumococcal disease is high, and complete PCV programmes are cost-effective, even in low-income countries.5Saokaew S Rayanakorn A Wu DB Chaiyakunapruk N Cost effectiveness of pneumococcal vaccination in children in low-and middle-income countries: a systematic review.Pharmacoeconomics. 2016; 34: 1211-1225Crossref PubMed Scopus (33) Google Scholar Undoing the nascent progress in preventing pneumococcal disease, especially in infants in resource-poor settings, would be regrettable. SP declares no competing interests. MvdL declares grants and speaker's fees from Pfizer, and personal fees from GSK, Merck, and Sanofi Pasteur MSD outside the submitted work. Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trialOur findings show that for nine of the 13 serotypes in PCV13, post-booster responses in infants primed with a single dose are equivalent or superior to those seen following the standard UK 2 + 1 schedule. Introducing a 1 + 1 schedule in countries with a mature PCV programme and established herd immunity is likely to maintain population control of vaccine-type pneumococcal disease. Full-Text PDF Open AccessWhen less is more: how many doses of PCV are enough?Pneumococcal conjugate vaccine (PCV) is an incredibly important, lifesaving vaccine, first licensed in 2000,1 and recommended for infant routine use in the UK in 2006.2 Since 2007 WHO has recommended it for inclusion in the routine infant immunisation schedule of all countries.3,4 Up to now, it has been rolled out in the national immunisation programmes of 141 countries (figure), has saved hundreds of thousands of lives,5 and is projected to save millions in the decades to come as country introductions continue and coverage increases. Full-Text PDF Open AccessReassessing the 1 + 1 pneumococcal conjugate vaccine schedulePneumococcal conjugate vaccines (PCVs) are approved and given to populations on the basis of large immunogenicity and safety databases after meeting strict prespecified immunological non-inferiority criteria in appropriately powered clinical studies. David Goldblatt and colleagues1 describe the response to a single dose of PCV in the first year of life followed by a booster in the second year (1 + 1 schedule), and compare this to the standard 2 + 1 schedule. Based on previous experience in the clinical setting, the results were not surprising. Full-Text PDF Reassessing the 1 + 1 pneumococcal conjugate vaccine schedule – Authors' replyStephanie Perniciaro and Mark Van der Linden, and Raul Isturiz and colleagues, are concerned that the post-booster endpoint in our 1 + 1 pneumococcal conjugate vaccine (PCV) 13 immunogenicity study1 is a poor indicator of direct protection during the first year of life. We agree, but the rationale for a 1 + 1 vaccine schedule is the maintenance of indirect protection through herd immunity, generated by sustained high coverage in the UK, first with PCV7 then with PCV13. Only 23 cases of PCV13-type invasive pneumococcal disease were identified in infants aged 2 years and younger in England and Wales in 2016–17,2 most of which were attributable to Streptococcus pneumoniae serotype 3, against which PCV13 does not provide either direct or indirect protection. Full-Text PDF