1 + 1 dose schedule for pneumococcal child vaccination: new normal?

The first pneumococcal conjugate vaccine (PCV), the 7-valent PCV, was introduced in the US child vaccination programme in 2000 and resulted in a substantial reduction in invasive pneumococcal diseases (IPD), particularly in children, but also in adults due to herd protection.1Musher DM Anderson R Feldman C The remarkable history of pneumococcal vaccination: an ongoing challenge.Pneumonia. 2022; 14: 5Crossref Google Scholar PCV7 was introduced in the USA, with a vaccination dose schedule 3 + 1 (vaccination at 2 months, 4 months, 6 months, and a booster between 12–15 months). In Europe a reduced 2 + 1 dose schedule was chosen based on data from immunogenicity studies and the fact that the vaccination schedule could be built in within the existing child vaccination programme.2Goldblatt 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 (81) Google Scholar Since then, several new PCVs have been made available covering a limited number of the estimated 100 known distinct serotypes.1Musher DM Anderson R Feldman C The remarkable history of pneumococcal vaccination: an ongoing challenge.Pneumonia. 2022; 14: 5Crossref Google Scholar The vaccination dose schedule for children younger than 2 years has been a topic of discussion, particularly for PCV10 and the PCV13. Several studies have shown that within the first year of life, similar immunogenicity was reached using the vaccination dose schedules 3 + 1, 3 + 0, and 2 + 1. WHO recommends for both the 10-valent pneumococcal protein D-conjugate vaccine (PHiD-CV, Synflorix; Brentford, UK) and the 13-valent PCV13 (Prevenar 13, Pfizer; New York NY, USA) either a 2 + 1 or 3 + 0 dose schedule.3WHOPneumococcal conjugate vaccines in infants and children under 5 years of age: WHO position paper—February 2019.Wkly Epidemiol Rec. 2019; 94: 85-104Google Scholar The International Vaccine Access Center provides a comprehensive overview of the different PCV vaccination schedules used worldwide. However, it has also been shown that 3 + 0 schedule does not lead to sustained antibody immunity beyond the first year of life, compared with schedules including booster vaccination. For that reason, Australia has changed their schedule from a 3 + 0 to a 2 + 1 schedule.4Swarthout TD Henrion MYR Thindwa D et al.Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study.Lancet Infect Dis. 2022; 22: 1737-1747Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 5Madhi SA Mutsaerts EAML Izu A et al.Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial.Lancet Infect Dis. 2020; 20: 1426-1436Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 6Licciardi PV Temple B Dai VTT et al.Immunogenicity of alternative ten-valent pneumococcal conjugate vaccine schedules in infants in Ho Chi Minh City, Vietnam: results from a single-blind, parallel-group, open-label, randomised, controlled trial.Lancet Infect Dis. 2021; 21: 1415-1428Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar In the UK in 2015, a reduced 1 + 1 dose schedule for PCV13 was suggested.7Flasche S Van Hoek AJ Goldblatt D et al.The potential for reducing the number of pneumococcal conjugate vaccine doses while sustaining herd immunity in high-income countries.PLoS Med. 2015; 12e1001839Crossref PubMed Scopus (44) Google Scholar A reduced pneumococcal vaccination dose schedule would reduce vaccination costs, reduce the pressure on an already complex child vaccination programme, and reduce the logistic problems of vaccinating children in remote settings.8Mackenzie GA Osei I Salaudeen R et al.A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to three-dose schedule of pneumococcal conjugate vaccination in rural Gambia: the PVS trial.Trials. 2022; 23: 71Crossref PubMed Scopus (5) Google Scholar, 9Temple B Tran HP Dai VTT et al.Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trial.Lancet Infect Dis. 2023; (published online April 13.)https://doi.org/10.1016/S1473-3099(23)00061-0Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Beth Temple and colleagues9Temple B Tran HP Dai VTT et al.Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trial.Lancet Infect Dis. 2023; (published online April 13.)https://doi.org/10.1016/S1473-3099(23)00061-0Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar reported, from a trial in Viet Nam, that a 1 + 1 PCV dose schedule greatly reduced vaccine-type carriage, probably generated substantial herd protection, and provided some degree of individual protection during the first year of life. They found that the 1 + 1 schedule is suitable for mature PCV programmes or for introduction in conjunction with a comprehensive catch-up campaign in settings where more complex vaccination schedules are difficult to implement. With this study from Asia, together with previous studies from South Africa5Madhi SA Mutsaerts EAML Izu A et al.Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial.Lancet Infect Dis. 2020; 20: 1426-1436Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar and England,2Goldblatt 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 (81) Google Scholar it has now been documented in three very different settings, that a 1 + 1 PCV vaccination schedule can be implemented in countries with mature PCV programs. Additionally, a trial in rural Gambia has been planned,8Mackenzie GA Osei I Salaudeen R et al.A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to three-dose schedule of pneumococcal conjugate vaccination in rural Gambia: the PVS trial.Trials. 2022; 23: 71Crossref PubMed Scopus (5) Google Scholar evaluating and comparing a 1 + 1 schedule with a 3 + 0 schedule. Although new PCV vaccines such as the 10-valent PCV from India (Pneumosil, Serum Institute of India; Pune, India) have a low cost per vaccination,10Adigweme I Futa A Saidy-Jah E et al.Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial.Lancet Infect Dis. 2023; (published online Jan 10.)https://doi.org/10.1016/S1473-3099(22)00734-4Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar this alone will not help with the issues of the complex child vaccination programmes and the logistics in repeated vaccination of children in particularly remote settings. The increasing data supporting a 1 + 1 schedule for pneumococcal child vaccination suggests that considering this dose schedule could be a safe and valid option. However, before deciding to reduce a place's pneumococcal child vaccination schedule from WHO recommended schedules of either 2 + 1 or 3 + 0 dose schedules3WHOPneumococcal conjugate vaccines in infants and children under 5 years of age: WHO position paper—February 2019.Wkly Epidemiol Rec. 2019; 94: 85-104Google Scholar to a 1 + 1 schedule, it is advisory to evaluate if the setting has an advanced enough PCV vaccination programme.2Goldblatt 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 (81) Google Scholar, 5Madhi SA Mutsaerts EAML Izu A et al.Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial.Lancet Infect Dis. 2020; 20: 1426-1436Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 9Temple B Tran HP Dai VTT et al.Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trial.Lancet Infect Dis. 2023; (published online April 13.)https://doi.org/10.1016/S1473-3099(23)00061-0Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar In conclusion, a 1 + 1 PCV vaccination schedule has been evaluated in different settings representing three regions in the world: Asia, Africa, and Europe. All sites have shown substantial protection using the 1 + 1 schedule compared with schedules including more than two vaccinations. Additional studies evaluating the 1 + 1 dose schedule for PCV can be expected soon, among them the planned trial in Gambia,8Mackenzie GA Osei I Salaudeen R et al.A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to three-dose schedule of pneumococcal conjugate vaccination in rural Gambia: the PVS trial.Trials. 2022; 23: 71Crossref PubMed Scopus (5) Google Scholar which will further help decision makers around the world to re-evaluate their local PCV vaccination guidelines and consider a 1 + 1 schedule, releasing savings for other relevant health priorities and simplifying logistics. Based on the already published studies, the 1+1 dose schedule for pneumococcal child vaccination might be the new normal soon. For a map of different PCV vaccination schedules see https://view-hub.org/map/?set=current-dosing-schedule&group=vaccine-introduction&category=pcv For a map of different PCV vaccination schedules see https://view-hub.org/map/?set=current-dosing-schedule&group=vaccine-introduction&category=pcv H-CS is a part of a Pfizer supported pneumococcal carriage project and participates in Merck, Sharpe and Dohme consultations. KF declares no competing interests. Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trialA 1 + 1 PCV schedule greatly reduces vaccine-type carriage and is likely to generate substantial herd protection and provide some degree of individual protection during the first year of life. Such a schedule is suitable for mature PCV programmes or for introduction in conjunction with a comprehensive catch-up campaign, and potentially could be most effective given as a mixed regimen (PCV10 then PCV13). A 0 + 1 PCV schedule has some effect on carriage along with a reasonable immune response and could be considered for use in humanitarian crises or remote settings. Full-Text PDF Open Access