Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children.     

Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent pneumococcal conjugate vaccine

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3?+?0 schedule (doses at 6, 10 and 14?weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5–8?week old infants (n?=?1000) and 12–23?month old children (n?=?1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12–23?months (adjusted prevalence ratio [aPR] 0.77 [0.61–0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89–1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43–1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85–1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p?<?0.001). In 12–23?month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p?=?0.004 and p?<?0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.     

Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England

Background/Aims

In April 2010 the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent PCV. We investigated pneumococcal carriage in children eligible for PCV7 or PCV13 and their household contacts.

Methods

Eligible families in Hertfordshire and Gloucester were identified and a nasopharyngeal swab obtained from consenting household members between July 2012 and March 2013. Samples were cultured for Streptococcus pneumoniae and serotyped by standard methods. For each serotype the ratio of its prevalence in invasive pneumococcal disease (IPD) to its carriage prevalence (case:carrier ratio, CCR) was calculated. Results were compared with previous carriage studies in 2001/2002 and 2008/2009, before and after PCV7 introduction.

Results

217 households were included. Among <5-year olds 47.7% (95% confidence interval 41.8–53.5) were carrying a pneumococcus compared with 51.0% (95% CI: 44.0–58.0) in 2008/2009 and 48.4% (95% CI: 44.1–52.7) in 2001/2002. The odds of carrying a PCV7 serotype was significantly reduced in 2008/2009 (0.07, 95% CI: 0.03–0.16) and 2012/2013 (0.01 95% CI: 0.00–0.07) relative to 2001/2002, while the odds of carrying any of the extra six PCV13 serotypes increased after PCV7 introduction (1.38, 95%CI: 0.73–2.59) but declined significantly after PCV13 introduction (0.05, 95%CI: 0.01–0.37). The CCRs for the frequently carried serotypes were relatively low, with the highest CCR observed for serotypes 7F, 19A, 3, 8, and 33F. Across the three carriage studies, CCR estimates were stable for nearly all serotypes.

Conclusion

Carriage of additional PCV13 serotypes has rapidly reduced post-PCV13 introduction in both vaccinated and unvaccinated individuals with a continued decline in transmission of PCV7 serotypes. Carriage rates in children remain unchanged, but the low CCRs of replacing serotypes would be expected to further reduce overall IPD across all age groups.     

Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia

Background

In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction.

Methods

Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005–2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed.

Results

Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p = 0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p < 0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15 C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p < 0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p = 0.02).

Conclusions

A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.     

Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older

Background

Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations.

Methods

This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50–64 years in which adults 60–64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50–59 were given PCV13. In this follow up study conducted about 4 years later, the 60–64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50–59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination.

Results

A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes.

Conclusion

In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses.     

Effect of the introduction of pneumococcal conjugate vaccines on serotype prevalence in Kuwait and Saudi Arabia

BackgroundStreptococcus pneumoniae infection is a major cause of morbidity and mortality. Although pneumococcal disease burden in Kuwait and Saudi Arabia is considered high, comprehensive surveillance data on pneumococcal conjugate vaccine (PCV) effects are lacking.MethodsSterile isolates from patients in Kuwait (2003–2016) and Saudi Arabia (aged ≤5 years, 2000–2010; all patients, 2011–2015) were included. Serotyped isolates were classified by inclusion in the 7-valent (PCV7) or 13-valent PCV (PCV13); isolates of other serotypes were classified as “non-PCV13”. Isolate frequency (number of isolates/year) and classification of isolates according to vaccine type were assessed by period (before PCV, after PCV7, and after PCV13 introduction).ResultsIn Kuwait, the frequency of collected isolates was highest after PCV7 introduction. Decreased frequency of PCV7 serotypes was seen after PCV13 introduction compared with before PCV and after PCV7 introduction. Increased frequency of the 6 additional serotypes in PCV13 and non-PCV13 serotypes was observed after PCV7 introduction with a subsequent decrease in the 6 additional serotypes in PCV13 and non-PCV13 serotypes after PCV13 introduction. The percentage of isolates of vaccine serotypes in Kuwait decreased over time. In Saudi Arabia, the frequency of collected isolates was highest after PCV7 introduction. An increased frequency of PCV7 serotypes was observed after PCV7 introduction, with a further decrease after PCV13 introduction. For the 6 additional serotypes in PCV13, an increased frequency was seen after PCV7 and PCV13 introduction compared to before PCV introduction. For non-PCV13 serotypes, an increased frequency was observed after PCV13 introduction compared to after PCV7 introduction. The percentage of isolates covered by PCV13 serotypes was similar across periods, while a substantial decrease in isolates covered by PCV7 was seen after PCV13 introduction.ConclusionPCVs in Kuwait and Saudi Arabia resulted in decreased frequency of some vaccine serotypes and an emergence of some non-PCV13 serotypes. Further investigation is warranted.     

Progressive changes in pneumococcal carriage in children attending daycare in Portugal after 6 years of gradual conjugate vaccine introduction show falls in most residual vaccine serotypes but no net replacement or trends in diversity

Objectives

To track ongoing trends in pneumococcal (Sp) serotype carriage under the selection pressure of moderate pneumococcal conjugate vaccine (PCV) use, children in a community in Portugal were studied in the same months in 3 consecutive years.

Methods

Nasopharyngeal specimens were collected (children aged 3 months to <7 years) in 8 urban daycare centers in February 2008 (n = 561) and 2009 (n = 585). Sp isolates were serotyped.

Results

While demographics were similar in 2008–2009 and a previously reported sample in 2007, PCV coverage (at least one dose) in the children studied rose from 76.5% to 84% although national coverage was lower than this. Sp carriage fell from 61% to 51% with a concomitant fall in PCV7 serotype carriage from 12.1% to 4.3%. Remaining PCV7 serotypes declined to near (23F) or totally (6B, 14) undetectable levels except 19F which persisted unchanged in around 4% of children. Although carriage of 3 and 6C rose, there was no net increase in non-PCV7 serotypes and no progressive trend in serotype diversity.

Conclusions

Ecological changes induced by PCVs where uptake is moderate appear to be different from high usage settings. We report falling Sp carriage due to PCV7 serotype disappearance with persistence of 19F and no ongoing net replacement after several years of PCV7 use and slowly rising uptake.     

Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule

Background

The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs.

Objective

To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule.

Methods

Studies were double-blind, randomized, active-controlled, multicenter studies except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4, and 6 months). The primary immunogenicity endpoint was the proportion of participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G concentrations ≥0.35 μg/mL (i.e., responders) 1 month postdose 2. Pneumococcal IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and concomitant vaccine responses were assessed.

Results

PCV13 and PCV7 elicited comparable immune responses for the 7 common serotypes after 2 infant doses. The proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6 additional serotypes, except common serotypes 6B (27.9–81.4%) and 23F (55.8–77.5%) and additional serotypes 3 (73.8–96.9%) and 6A (79.2–94.4%). Serotypes 6B and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated functional activity; >95% of participants achieved OPA levels ≥1:8 postdose 2. Concomitant vaccine responses were similar between PCV13 and PCV7 groups.

Conclusion

Immune responses elicited by PCV13 following 2 infant doses support transition from PCV7 to PCV13 in countries using a 2+1 schedule.Clinical trial registration numbers: UK (Study 007) NCT00384059; Italy (Study 500) NCT00366899; Spain (Study 501) NCT00368966; Spain (Study 3007) NCT00474539; and Mexico (Study 3009) NCT00708682.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults

Background

Streptococcus pneumoniae is a major cause of morbidity and mortality among adults 50 years of age and older in the United States. Pneumococcal conjugate vaccines are efficacious against pneumococcal disease in children and may also offer advantages in adults.

Methods

We performed a randomized, modified double-blind trial that compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60–64 years of age. An additional group of 403 adults 50–59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination.

Results

In the randomized trial, the month 1 post-vaccination OPA geometric mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines and for serotype 6A, a serotype unique to PCV13, and were comparable for the other 4 common serotypes. The immune response to PCV13 was generally greater in adults 50–59 years of age compared to adults 60–64 years of age. OPA titers declined from 1 month to 1 year after PCV13 administration but remained higher than pre-vaccination baseline titers.

Conclusions

PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection.     

Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine

Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval −18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period.     

The effect of an alternative reduced-dose infant schedule and a second year catch-up schedule with 7-valent pneumococcal conjugate vaccine on pneumococcal carriage: a randomized controlled trial

Background

The 7-valent pneumococcal conjugate vaccine (PCV7) was initially licensed for use as 3 infant doses and a booster (3 + 1). However, 2 infant doses plus a booster schedules only (2 + 1) are widely used. We compared the effect of these two schedules on pneumococcal carriage in young children. We also assessed the effect of a 2-dose schedule in the second year (“catch-up” schedule; 0 + 2).

Methods

Subjects (n = 733) were randomized to the 2 + 1 (4, 6, 12 m), 3 + 1 (2, 4, 6, 12 m) or 0 + 2 (12, 18 m) schedules. Blood samples for serotype-specific IgG (SSIgG) determination were obtained at 2, 7, 13, 19 months, and nasopharyngeal + oropharyngeal pneumococcal cultures were obtained at 2, 4, 6, 7, 12, 13, 18, 19, 24, 30 months.

Results

After primary infant PCV7 series, SSIgG was significantly lower for four out of seven serotypes in children receiving 2 doses compared to 3 doses, particularly for serotypes 6B and 23F. This was associated with a higher acquisition and prevalence rates of vaccine serotype carriage in the 2-dose group, particularly serotypes 6A and 6B. After the booster dose at 12 months of age, most differences were not significant anymore. A single PCV7 dose at age 12 months in previously unvaccinated subjects (“catch up” schedule) resulted in poor SSIgG concentrations for three out of seven serotypes, resulting in higher acquisition and prevalence rates of vaccine serotypes (grouped) compared to infants receiving a booster dose at 12 months (2 + 1 and 3 + 1 groups). Similarly, serotypes 6B and 6A also showed significantly higher carriage rates after a single dose at 12 months. After the second catch-up dose at 18 months, the rates were similar to those in the 2 + 1 or 3 + 1 schedules, except for serotype 6A.

Conclusions

Three infant doses seem to better protect against PCV7-serotype acquisition and carriage than two. However, after booster, most of these differences disappear. A 2-dose second year catch-up campaign may enhance the reduction of PCV7-serotype spread in the community.     

Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children

Background

Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

Objective

To characterize immune responses to 13-valent pneumococcal CRM₁₉₇ conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal–meningococcal C-CRM₁₉₇ conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

Methods

Children (n = 89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002–2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n = 50) and PCV9/PCV13 (n = 39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

Results

One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35 μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

Conclusions

PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.     

Pneumococcal carriage in children in Ulaanbaatar,Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine

BackgroundNasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia.MethodsWe conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5–8 weeks old) and 989 children eligible for vaccination (12–23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray.FindingsOne year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12–23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39–0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30–1.85]), compared with the pre-PCV period. In 5–8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33–0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83–1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed.ConclusionThis study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring.     

Comparison of serologic responses to vaccination with one dose or two doses of 7-valent pneumococcal conjugate vaccine in HIV-infected adult patients

Background

Vaccination with 7-valent pneumococcal conjugate vaccine (PCV) has been shown to decrease the incidence of recurrent invasive pneumococcal disease among HIV-infected adults in Africa. Longitudinal follow-up studies of serologic responses to different doses of 7-valent PCV are rarely performed in HIV-infected adult patients receiving combination antiretroviral therapy (cART).

Methods

From October 2008 to June 2010, 115 CD4-matched pairs of HIV-infected patients aged ≥20 years who had no prior pneumococcal vaccination received one or two doses of 7-valent PCV. Anticapsular antibodies against 4 serotypes (6B, 14, 19F, and 23F) were examined at the 12th, 24th, 36th, and 48th week following vaccination. Significant antibody responses were defined as ≥2-fold increase in the IgG level plus a post-vaccination antibody level ≥1000 ng/ml.

Results

The most common reported adverse effects were injection site soreness (19.3%) and pain (4.8%). Significant antibody response rate was highest for serotype 14, followed by 23F, 19F, and 6B in all of the four time points examined. At week 48, patients who received two doses of 7-valent PCV had a significantly higher response rate to serotype 6B (P = 0.03) and 23F (P = 0.01) than those who received one dose; moreover, the former group also had a higher response rate to at least one (P = 0.03) and two serotypes (P = 0.02) in intention-to-treat analysis than the latter group.

Conclusions

HIV-infected adult patients on cART who received two doses of 7-valent PCV achieved better serological responses to at least one serotype than those who received one dose during the 48 weeks of follow-up.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Background

The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13).

Methods

We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination.

Results

Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment.

Conclusion

In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13.     

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study

Background

In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected.

Methods

Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003–2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007–2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively.

Findings

The proportion of PCV7 serotypes among all IPD cases (n = 7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P < 0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P = 0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P = 0.008), 19A (P = 0.03) and 19F (P = 0.005), compared to serotype 1 and 7F.

Conclusion

There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.     

Comparison between a new multiplex electrochemiluminescence assay and the WHO reference enzyme-linked immunosorbent assay to measure serum antibodies against pneumococcal serotype-specific polysaccharides

Background

Two electrochemiluminescence (ECL) assays were developed which, together, can simultaneously measure serum antibodies against pneumococcal capsular polysaccharides (PnPS) for 17 serotypes. The assays were validated for the 13 PnPS included in the 13-valent pneumococcal conjugate vaccine (PCV13). As recommended by the World Health Organization (WHO), we compared the ECL assays with the WHO reference enzyme-linked immunosorbent assay (ELISA) and derived a threshold corresponding to the 0.35?µg/mL threshold established for the WHO reference ELISA for the non-inferiority comparison and licensure of new PCVs against invasive pneumococcal disease.

Evolution of serotypes in bacteremic pneumococcal adult pneumonia in the period 2001–2014, after introduction of the pneumococcal conjugate vaccine in bizkaia (spain)

The introduction of pneumococcal conjugate vaccines (PCV7 and PCV13) in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease in adults. The aim of this study is to analyze the distribution of pneumococcal serotypes in adults with bacteremic pneumococcal community-acquired pneumonia (BPP) after the introduction of PCVs in childhood, and the impact of age and comorbidity on this distribution. We conducted an observational study of all adults hospitalized with BPP between 2001 and 2014, in two tertiary hospitals. Overall, we identified 451 cases of BPP (2001–2005: 194, 2006–2010: 134, 2011–2014: 123). The rate of appearance of new cases decreased over the study period. In 70% of the cases, the serotypes found were among those included in PCV13. The most prevalent serotypes were 3 (23.1%), 7F (14.6%), 19A (8.4%) and 1 (7.5%). There was a significant trend to decrease in the percentage of BPP cases due to PCV7 from period 2001–2005 to 2011–2014 (p = 0.0166) and a significant trend to increase in the six serotypes added to form PCV 13 (p = 0.0003). Serotype 3 was the most frequent in patients who developed complications during hospitalization. We did not detect a significant increase in cases caused by non-PCV13 serotypes. The most frequent non-PCV13 serotype was 22F. In conclusion, a significant proportion of adults continue to develop BPP with vaccine serotypes despite infant pneumococcal vaccination. There is a need for further strategies to reduce the current burden of this disease on adults.     

Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine

13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.     

Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.