Background: The burden of pneumococcal diseases remains high in Japan. Pn-MAPS24v is a novel MAPS-based vaccine containing complexes of 24 serotype-specific polysaccharides (PS), non-covalently coupled with fusion protein 1 (CP1). This study evaluated the safety and immunogenicity of different dose levels of Pn-MAPS24v, administered in Japanese adults either subcutaneously (SC) or intramuscularly (IM). Methods: In this phase 1, dose-escalation, observer-blind trial conducted in Japan, 54 pneumococcal vaccinena & iuml;ve adults aged 20-49 years (stage 1), and 72 adults aged 65-85 years (stage 2) were sequentially enrolled. In stage 1, participants were randomized 1:1 (SC:IM) to receive a single Pn-MAPS24v dose at one of the dose levels (1 mu g, 2 mu g, or 5 mu g per PS). In stage 2, participants were randomized 3:1 (Pn-MAPS24v:23-valent pneumococcal polysaccharide vaccine [PPSV23]) and 1:1 (SC:IM) to receive a single dose of either Pn-MAPS24v (one of three dose levels), or PPSV23. Solicited adverse events (AEs) were collected through 7 days post-vaccination, and treatment-emergent AEs (TEAEs) up to 1 month post-vaccination. Serotype-specific opsonophagocytic activity titers and immunoglobulin G (IgG) concentrations, as well as anti-CP1 IgG concentrations were measured before and 1 month post-vaccination. Results: No safety or reactogenicity concerns were identified in any age category across groups. No grade 3-4 TEAEs, serious AEs, or deaths were reported. Regardless of the age category, dose level, administration route, or study vaccine, the frequency of reported TEAEs was low and all vaccine-related TEAEs were mild. Pain, tenderness, and fatigue were the most frequently reported solicited AEs. One month post-vaccination, PnMAPS24v induced serotype-specific immune responses that were comparable or higher than those elicited by PPSV23. The immune responses were similar after SC and IM administration. Conclusion: Pn-MAPS24v showed an acceptable safety profile and was immunogenic after SC and IM adminis- tration, therefore supporting the further development of Pn-MAPS24v in Japan. ClinicalTrials.gov: NCT04265911

Introduction:Widespread implementation of pneumococcal conjugate vaccines (PCVs)-namely the 7-valent PCV (PCV7), 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), and 13-valent PCV (PCV13)-in infant national immunization programs has reduced pneumococcal diseases in children, including invasive pneumococcal disease (IPD), acute otitis media (AOM), and community-acquired pneumonia (CAP). However, as the use of PCV impacts pneumococcal epidemiology, identifying the serotypes associated with remaining disease is crucial to guide future vaccination strategies for this population. Methods:We systematically searched the literature for observational studies (2006-2020) on pneumococcal serotype distribution in IPD, AOM, and CAP among ≤5-year-old children post-PCV introduction. Serotype-specific pooled percentage averages were calculated by post-PCV period (post-PCV7 or pooled post-PHiD-CV/PCV13), or by PCV product (PHiD-CV or PCV13) to determine the contribution of each serotype to a certain clinical manifestation. Results:Our analysis of 86 studies (47 on IPD, 30 on AOM, and 9 on CAP) shows continued reporting of several vaccine serotypes in all clinical manifestations post-PHiD-CV/PCV13, particularly serotypes 19A, 3, and 1. In PCV13 settings, serotype 19A reporting was reduced but still prevalent compared to PHiD-CV settings. Predominant non-PCV13 serotypes varied by clinical manifestation. Conclusion:Post-PCV implementation, pneumococcal epidemiology in children is intricate. The persistence of some vaccine serotypes, variations across clinical manifestations, rising antimicrobial resistance, and other factors highlight the need for new vaccine technologies providing enhanced and broader protection to children.

Background: Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/ 20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers. Methods: In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 mu g/2 mu g/5 mu g per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed. Results: Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 mu g/2 mu g/5 mu g: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 mu g/2 mu g/5 mu g and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of PnMAPS24v 1 mu g/2 mu g/5 mu g recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, >= 93 % of participants in each group had IgG concentrations >= 0.35 mu g/mL; >92 % had OPA titers >= lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, >= 78 % of Pn-MAPS24v recipients in each group had IgG concentrations >= 0.35 mu g/mL and 80 %-100 % had OPA titers >= LLOQ. Conclusions: In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. PnMAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants.

Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported >= 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006. Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9-45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified

Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and oropharynx. In 2016, the bivalent HPV-16/18 vaccine was included in the Korea National Immunization Program. This vaccine protects against HPV types 16 and 18 and other oncogenic HPV types predominant in cervical and anal cancers. This post-marketing surveillance (PMS) study assessed the safety of the HPV-16/18 vaccine in Korea. The study was conducted in males and females aged between 9 and 25 years, from 2017 to 2021. Safety was measured in terms of frequency and intensity of adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) after each vaccine dose. The safety analysis included all participants who were vaccinated as per prescribing information and who completed a 30-day follow-up after at least one dose. Data were collected using individual case report forms. The total safety cohort included 662 participants. A total of 220 AEs were reported in 144 subjects (21.75%), and there were 158 ADRs in 111 subjects (16.77%), with the most common being injection site pain in all cases. No SAEs or serious ADRs were reported. Most AEs were reported after the first dose and were injection site reactions with mild intensity that recovered. No individuals required hospitalization or an emergency department visit. Safety results showed that the HPV-16/18 vaccine was generally well tolerated in the Korean population, and no safety concerns were identified.ClinicalTrials.gov Identifier: NCT03671369.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Background Cervical cancer is the third most frequent cancer in Chinese women aged 15-44 years old. Human papillomavirus (HPV) is recognized as the main etiologic agent of cervical carcinomas. This study aims to better understand the natural history of HPV infections in Chinese women aged 18-25 years. Research Design and Methods Data from 3,025 control arm women (AS04-HPV-16/18 vaccine trial) were analyzed to assess the probability of progression or clearance from a 6-month persistent infection (6MPI) to a cervical intraepithelial neoplasia grade 2 or greater (CIN2+), and the association with clinical determinants. Data were analyzed using univariate and multivariable Cox models. Results A total of 1,324 women with 3,814 HPV infections were included, and 65.7% of the women had at least one 6MPI. Among those 6MPI, 5.0% progressed to CIN2+, while 61.0% cleared within 6 months. The risk of progression from 6MPI to CIN2+ was substantially higher for oncogenic versus non-oncogenic HPV types. Conclusions Oncogenic HPV infections showed lower clearance and higher risk to progress to CIN2 +. These findings observed in a population of Chinese women, confirmed previous findings from multinational studies.

INTRODUCTION:The pivotal efficacy study assessed efficacy and safety of GSK's AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years up to 6 years. The present extension study, performed 4 years later, offered AS04-HPV-16/18 vaccination to placebo recipients. Vaccine safety and its long-term protective effect were assessed at Year 10.METHODS:All 6051 women who received AS04-HPV-16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open-label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three-dose AS04-HPV-16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV-16/18 and other oncogenic types was assessed as exploratory objective.RESULTS:Among 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04-HPV-16/18 and reported no serious adverse events, potential immune-mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV-16, -18, and -16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5-89.7), 79.8% (64.5-89.2), and 80.8% (72.4-87.0), respectively. VE against HPV-16/18 ASC-US+, CIN1+, and CIN2+ was 92.7% (82.2-97.7), 94.8% (67.4-99.9), and 90.5% (34.6-99.8), respectively.CONCLUSION:AS04-HPV-16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long-term protection similar to other efficacy trials worldwide.

Background In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes. Methods Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009―2011. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010―2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5―7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010. Results From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years. Conclusions This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.

As a stepping stone toward evaluation in infants, the safety and immunogenicity of an investigational 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (12vPHiD-CV) was assessed in toddlers. 12vPHiD-CV contains CRM197-conjugated capsular polysaccharides of serotypes 6A and 19A in addition to capsular polysaccharides of the 10 serotypes in PHiD-CV. In this phase I, double-blind, multicenter study (NCT01485406) conducted in Germany, 61 healthy toddlers aged 12–23 months previously primed with three PHiD-CV doses were randomized (1:1) to receive one dose of 12vPHiD-CV or PHiD-CV. Safety and reactogenicity of 12vPHiD-CV were assessed in terms of occurrence of grade 3 vaccination-related solicited and unsolicited adverse events (AEs) and vaccination-related serious AEs. Immune responses were evaluated 1 month post-vaccination. Grade 3 solicited local AEs (all considered vaccination-related) were reported for two (6.5%, redness) and three (9.7%, swelling) toddlers in the 12vPHiD-CV group and one (3.4%, swelling) in the PHiD-CV group. Grade 3 vaccination-related solicited general AEs were only reported in the PHiD-CV group. No grade 3 unsolicited or serious AEs were reported. For PHiD-CV serotypes, 100% of toddlers in both groups had antibody concentrations ≥0.2 µg/mL 1 month post-vaccination, and antibody geometric mean concentrations increased from pre-boosting. For serotypes 6A and 19A, antibody responses tended to be higher in the 12vPHiD-CV than the PHiD-CV group. A single dose of 12vPHiD-CV administered in toddlers was well tolerated and no safety concerns were identified. Immune responses were comparable to those induced by PHiD-CV when administered in toddlers previously primed with three doses of PHiD-CV.

In 9-17-year-old Chinese girls, the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18) given as three-dose schedule induced high antibody levels, which were noninferior 1 month after the third dose to those observed in 18-25-year-old Chinese women in a large efficacy study. We assessed the persistence of antibodies 8-9 years after vaccination in the same subjects.This follow-up phase III, open-label study (NCT03355820) included subjects who had received three doses of AS04-HPV-16/18 in the initial trial (NCT00996125). Serum antibody concentrations were assessed by ELISA and compared to antibody persistence observed in 18-25-year-old Chinese women 6 years after first vaccination in the efficacy study (NCT00779766).Out of the 227 enrolled subjects, 223 were included in the per-protocol immunogenicity analysis. Mean interval from first AS04-HPV-16/18 dose to blood sampling was 101.4 months (8.5 years). For antibodies against HPV-16 and -18, 8.5 years after first vaccine dose all subjects remained seropositive and antibody. Geometric mean concentrations (GMCs) were 1236.3 (95% confidence interval [CI]: 1121.8; 1362.4) and 535.6 (95% CI: 478.6; 599.4) ELISA Units/mL, respectively. These seropositivity rates and antibody GMCs were higher than those observed 6 years after first vaccination of 18-25-year-old women.Sustained anti-HPV-16 and -18 immune responses were observed 8-9 years after AS04-HPV-16/18 vaccination of 9-17 year-old Chinese girls that were higher than the ones observed 6 years after first vaccination in Chinese adult women in whom AS04-HPV-16/18 efficacy against cervical intraepithelial neoplasia of grade ≥2 was demonstrated.

Plain Language Summary Focus on the patient What is the context? Infant immunization programs worldwide include the pneumococcal conjugate vaccines Synflorix and Prevnar 13 to help combat pneumococcal diseases. Countries or regions choose whether to use Synflorix or Prevnar 13 and may decide to switch from one vaccine to the other. This can result in infants receiving a mixed vaccination regimen. Limited information is available about such mixed regimens. What is new? We assessed the immunogenicity of three infant vaccination regimens: 1) priming with two doses of Prevnar 13 and boosting with Synflorix; 2) priming with one dose of Prevnar 13 followed by one dose of Synflorix and boosting with Synflorix; 3) priming and boosting with Synflorix. The study showed that: Switching from Prevnar 13 to Synflorix at any time during the vaccination regimen did not seem to affect safety. When switching from Prevnar 13 to Synflorix at the time of boosting, immunogenicity was mostly similar to that of the Synflorix- only regimen. Switching vaccines during priming resulted in a trend toward lower immune responses for some vaccine components. What is the impact? This piece of evidence can be considered by doctors and health authorities when evaluating the possibility of switching pneumococcal vaccines in an immunization program or individual immunization regimen. Further effectiveness studies from countries or regions switching from Prevnar 13 to Synflorix (or vice versa) may shed more light on the feasibility of switching between these vaccines. Background: We assessed the safety and immunogenicity of 2 + 1 infant regimens initiated with the 13-valent pneumococcal conjugate vaccine (PCV13) and completed with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV). Methods: This partially blinded study randomized 6-12-week-old infants to receive two-dose priming and a booster (at ages 2, 4, 12-15 months) with: PCV13 at priming and PHiD-CV at boosting (PPS); PCV13 then PHiD-CV at priming and PHiD-CV at boosting (PSS); or PHiD-CV at priming and boosting (SSS control). All analyses were descriptive, i.e., no statistical significance tests were done. Results: The total vaccinated cohort at priming comprised 294 infants. Grade 3 adverse events were reported after 8.7% (PPS), 11.4% (PSS), and 16.9% (SSS) of primary doses (primary objective). No serious adverse events were considered vaccination-related. For most PHiD-CV serotypes, observed percentages of children reaching antibody concentrations >= 0.2 mu g/mL and opsonophagocytic activity (OPA) titers above cutoffs were similar across groups 1 month post-priming and post-booster. Observed geometric mean antibody concentrations and OPA titers were lower for some PHiD-CV serotypes with the mixed regimens than with PHiD-CV only, especially for PSS. However, no tests of statistical significance were performed. Conclusions: Immunogenicity of the two mixed PCV13/PHiD-CV regimens seemed mostly similar to that of a PHiD-CV-only series, although observed antibody GMCs and OPA GMTs for some PHiD-CV serotypes were lower. No safety concerns were raised. The clinical relevance of the observed differences is unknown.

Background: Nasopharyngeal carriage (NPC) of Streptococcus pneumoniae is a precondition for pneumococcal disease and a source of transmission. This trial evaluated NPC of S. pneumoniae and other pathogens post-vaccination with the pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) South African children. Methods: In this phase III, open, single-centre, controlled study (ClinicalTrials.gov: NCT00829010), 484 children were stratified by HIV status: 83 HIV+, 101 HEU, and 300 HUU. HIV+ and HEU children received a 3 + 1 PHiD-CV vaccination schedule: primary vaccination, age 6110/14 weeks, and booster dose, age 9-10 months. HUU infants were randomised (1:1:1) to 3-dose priming and booster (HU11/3+1); 3-dose priming without booster (HUU/3+0); or 2-dose priming and booster (HUU/2+1). Bacterial NPC was assessed 8 times up to 24-27 months of age. Results: Overall pneumococcal carriage rates were similar across 3+1 groups irrespective of HIV status; trends towards higher carriage rates in the HIV+ than HEU and HUU/3+1 groups were observed at 24-27 months of age. In HUU children, carriage of any pneumococcal serotype was similar for the three different dosing schedules at all timepoints; carriage of vaccine-type pneumococci tended to be lower at 16-19 months and 24-27 months of age in children who had received a booster dose (HUU/2+1 and HUU/3+1 groups) than in the HUU/3+0 group. Carriage rates of NTHi, Staphylococcus aureus and Moraxella catarrhalis were comparable between all groups. Conclusions: HIV infection or exposure did not seem to alter the effect of PHiD-CV on pneumococcal NPC in children during their first 2 years of life. NPC prevalence of vaccine-type pneumococci following vaccination series tended to be lower in children who had received a booster dose in comparison to those who had not. (C) 2020 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.

Background: We evaluated bacterial nasopharyngeal carriage (NPC) prevalence and cumulative acquisition following 7-valent pneumococcal conjugate vaccine (PCV7) or pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administration. Methods: Participants were children from two clinical trials in a South African center who received PCV7 (n = 250) or PHiD-CV (n = 100) at ~6 weeks, ~14 weeks, and ~9-10 months of age, and were enrolled between Dec2009-Apr2010 and Mar2009-May2010 in the PCV7 and PHiD-CV studies, respectively. Sample collection, most microbiological assessments, and data re-analysis methods were identical. Results: NPC prevalence of any pneumococcal serotype was 18.5% and 17.0% at pre-vaccination, and 63.1% and 67.3% in 24-27 month-old children among PCV7 and PHiD-CV recipients, respectively. In 24-27 month-old children, 96.1% and 99.0% of PCV7 and PHiD-CV recipients had acquired ≥1 pneumococcal serotype, 53.7% and 62.9% ≥1 PCV7 serotype, 1.5%, and 3.1% ≥1 of serotypes 1, 5 or 7F, 23.2% and 19.6% serotype 6A, 23.2% and 21.7% serotype 19A, 88.7%, and 91.0% H. influenzae, and 50.3% and 62.9% Staphylococcus aureus, respectively. Conclusions: This analysis of two concurrent clinical trials did not reveal differences in bacterial NPC prevalence or acquisition in PCV7- and PHiD-CV-vaccinated children. Trial registration: South African National Clinical Trial Register (NHREC DOH-27-0511-299); ClinicalTrials.gov (NCT00829010).

RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expanded Program of Immunization, infants 8–12 weeks old were randomized to receive either RTS,S/AS01E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile.

Background: No data are currently available on immunogenicity of higher-valent pneumococcal conjugate vaccines when co-administered with a 4-component meningococcal serogroup B vaccine (4CMenB). Methods: Post-hoc analysis of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) immunogenicity when co-administered with 4CMenB (2 + 1 schedule) and/or a CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) in a trial assessing 4CMenB reduced schedules and co-administration with MenC-CRM (NCT01339923). Infants were randomized to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM (Group 2) at 3, 5, and 12 months (M) of age. Both groups received PHiD-CV (3 + 1 schedule) as part of the Brazilian national immunisation programme at 3 M, 5 M, 7 M, and 12 M of age. Antibody responses were assessed pre-vaccination, 1 M post-dose 2, pre-booster, and 1 M post-booster. Results: Anti-pneumococcal antibody responses were in similar ranges in the two study groups. Conclusions: 4CMenB co-administration did not seem to impact antibody responses to PHiD-CV in infants. (C) 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.

Introduction: Evidence on the interchangeability between the two pediatric pneumococcal conjugate vaccines (PCVs) - pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV13) - is limited but growing. We performed a systematic literature review to summarize evidence for PHiD-CV/PCV13 interchangeability regarding immunogenicity, safety, and effectiveness against pneumococcal disease. Areas covered: Seven records disclosing results from six studies on PHiD-CV/PCV13 interchangeability were identified. Four clinical trials showed that mixed schedules with a PHiD-CV-to-PCV13 switch at boosting or a PCV13-to-PHiD-CV switch during priming or at boosting were immunogenic with no apparent safety concerns. Two observational studies in the context of a programmatic PHiD-CV-to-PCV13 switch showed similarly high effectiveness against overall invasive pneumococcal disease with a mixed PHiD-CV/PCV13 schedule and a PCV13-only schedule. No effectiveness data for a PCV13-to-PHiD-CV switch and no immunogenicity/safety/effectiveness data for a PHiD-CV-to-PCV13 switch during priming were found. Expert opinion: For epidemiological or programmatic reasons, several local/national authorities have switched PCVs in their immunization programs. Consequently, children have received mixed schedules. Although herd immunity may obscure the individual effect, the limited data are reassuring. Additional evidence from these settings - especially effectiveness or impact data - may provide the necessary information for authorities to make informed decisions on interchanging PCVs.

BACKGROUND:The burden of human papillomavirus (HPV) diseases is high in Latin America. HPV vaccines licensed from 2006 onwards offer protection against most HPV-related cancers, especially when introduced into national immunization programs. Barriers to optimal vaccine uptake are, however, lowering the impact of adolescent HPV vaccination programs. Immunization of children might overcome these barriers and be a strategy of choice for some countries. METHODS:This multicenter phase III randomized, controlled, single-blind study (NCT01627561) was conducted in Colombia, Mexico and Panama to assess safety and immunogenicity of 2-dose vaccination with AS04-adjuvanted HPV-16/18 vaccine in girls 4-6 years of age. We report safety outcomes and anti-HPV-16/18 antibody titers measured by enzyme-linked immunosorbent assay in HPV-vaccinated girls that were followed over a 36-month period. RESULTS:Over 36 months (ie, 30 months after the second vaccine dose), among 74 girls included in the HPV group, 1 serious adverse event unrelated to vaccination has been reported. No withdrawal because of (serious) adverse events has been reported. At month 36, all girls in the per-protocol-cohort were still seropositive for anti-HPV-16 and anti-HPV-18 with geometric mean concentrations of 1680.6 and 536.4 enzyme-linked immunosorbent assay units/mL, respectively. CONCLUSIONS:The AS04-adjuvanted HPV-16/18 vaccine administered according to a 2-dose schedule to girls 4-6 years of age induced a high and sustained immunologic response with an acceptable safety profile during the 30 months following vaccination.