Response to: Pneumococcal conjugate vaccines in Latin America: are PCV10 and PCV13 similar in terms of protection against serotype 19A?

Dear Editor,

We agree with one of the conclusions of the Editorial titled ‘Pneumococcal conjugate vaccines in Latin America: are PCV10 and PCV13 similar in terms of protection against serotype 19A?’ written by Avila-Aguero et al. [1], describing that serotype 19A remains a circulating pathogen worldwide, requiring adequate surveillance in those countries which have considered the use of either PHiD-CV (pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine) or 13-valent pneumococcal conjugate vaccine (PCV13). This is in line with a recent systematic review which found that in the early years of high valent PCV use, serotype 19A represented 14.2% of the overall serotype invasive pneumococcal disease (IPD) contribution, while non-PCV13 serotypes contributed to 42.2% of childhood IPD cases [2]. However, the second conclusion is debatable. Evidence generated from well-designed noncomparative studies suggests that PCV13 does not offer a better protection than PHiD-CV against 19A IPD in the eligible vaccine cohorts. In fact, it was shown for both PCVs that the effectiveness/impact against 19A IPD appeared to be lower compared to other vaccine serotypes included in both products, such as 7F, which has been related to either severe or fatal outcome in children with IPD [3]. This would explain the circulation of 19A serotype in countries with PCVs in National Immunization Programs (NIP). This observation was made in studies conducted by independent investigators in different geographical settings. Moore et al. [4], in a matched case–control study carried out in the United States in children aged 2–59 months, documented a vaccine effectiveness (VE) of 1 or more dose of PCV13 as 85.6% (95% confidence interval [CI] 70.6; 93.5) against 19A IPD, which was lower than 96.5% (95% CI 82.7; 100) VE observed against 7F IPD. Weinberger et al. [5] conducted an indirect cohort analysis in children aged 4 and 56 months who received at least two doses of PCV13 before 12 months or one dose after 12 months. The study showed a VE of 83% (95% CI 41; 95) against 19A IPD and VE of 100% against IPD due to serotype 7F. An indirect cohort analysis carried out in Germany [6] in children aged 2–24 months, who received at least one dose of PCV13 from July 2010 till June 2015, showed a VE of 77% (95% CI 47; 90) and 84% (95% CI 18; 98) against IPD due to 19A and 7F, respectively. Likewise, an indirect cohort analysis conducted in children aged 4–56 months in the UK [7] showed a VE of 67% (95% CI 33; 84) against 19A IPD and 91% (95% CI 70; 98) against 7F IPD following PCV13 introduction. Similar trends were observed for PHiD-CV. A population-based observational study in Finland demonstrated a 62% (95% CI 20; 85) reduction in 19A IPD compared to a 92% (CI 95% 86; 95) reduction in vaccine type IPD, including 7F [8]. Similarly, in the Netherlands, where PHiD-CV was used in NIP since 2011, sentinel laboratory surveillance revealed a 62% (95% CI 23, 81) relative reduction of the incidence of 19A IPD and a 96% (95% CI 68; 99) relative reduction of 7F IPD in the PHiD-CV eligible cohort (children born from March 2011 to February 2014, ≥3 months of age, and given a diagnosis of IPD before June 2014) [9]. Finally, the unmatched case–control study that examined the sequential use of PCVs in Quebec, Canada, in children aged 2–59 months who received at least one dose of PCV showed VE of 71% (95% CI 24; 89) and 74% (95% CI 11; 92) against 19A IPD for PHiD-CV and PCV13, respectively [10]. VE for 7F was only assessed for PHID-CV and was 93% (95% CI 23; 99).

Summarizing these results, both PHiD-CV and PCV13 have not controlled absolutely the 19A IPD despite the effectiveness demonstrated for other serotypes (i.e. 7F). Regardless of differences in immunogenicity against serotype 19A shown by PCV13 containing this polysaccharide antigen and PHiD-CV which does not, protection against serotype 19A by PHiD-CV, through cross reactivity generated by the 19F serotype included in the vaccine was biologically plausible as it has been previously described [11,12]. Importantly, these data served as the basis for a clinical update and variation of the summary of product characteristics. Recently, an observational comparative study held in Sweden evaluating the impact of both PCVs on IPD in equivalent populations showed a trend for lower impact against 19A IPD in PHiD-CV using counties in vaccinated and non-vaccinated cohorts. However, a more pronounced increase of non-vaccine types (excluding serotype 6C) has been reported in older adults in counties using PCV13 in their NIP [13]. Indeed in the adult population ≥ 65 years, reductions on 19A IPD have been reported more consistently in PCV13 using countries. However, this observation is of relative importance in the context of overall incidence of IPD given that the majority of IPD in this vulnerable age-group is caused by non-vaccine types. As described, despite the vaccine introduction, serotype 19A remains a common serotype in older children and adults in most settings, irrespective of the vaccine used, schedule or geographical area [2,14]. We therefore agree with Avila-Aguero et al. [1] that further surveillance of IPD is warranted with special attention to 19A. However, more important is monitoring the trends on overall IPD and in non-vaccinated cohorts, since non-vaccine serotypes are becoming the predominant source of IPD. Therefore, it should be the focus of the continuing surveillance efforts and future vaccine development.

Declaration of interest

All authors are employed by the GSK group of companies and own stock options in GSK.

Additional information

Funding

GlaxoSmithKline Biologicals SA funded all costs associated with the development of this manuscript.