Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

Background: Cameroon’s suboptimal access to childhood vaccinations poses a significant challenge to achieving the Immunization Agenda 2030 goal—ranking among the top 15 countries with a high proportion of zero-dose (unvaccinated) children worldwide. There are clusters of zero-dose children in pockets of communities that traditionally miss essential healthcare services, including vaccination. The Manoka Health District (MHD) is home to such settlements with consistently low vaccination coverages (DPT-HepB-Hib-1: 19.8% in 2021) and frequent outbreaks of vaccine-preventable diseases (VPD). Therefore, the absence of literature on zero-dose children in this context was a clarion call to characterize zero-dose children in fragile settings to inform policy and intervention design. Methodology: This cross-sectional analytical study involved 278 children, 0–24 months of age, selected from a 2020 door-to-door survey conducted in the two most populous health areas in an archipelago rural district, MHD (Cap-Cameroon and Toube). We used R Statistical Software (v4.1.2; R Core Team 2021) to run a multivariable logistic regression to determine zero-dose associated factors. Results: The survey revealed a zero-dose proportion of 91.7% (255) in MHD. Children who were delivered in health facilities were less likely to be zero-dose than those born at home (AOR: 0.07, 95% CI: 0.02–0.30, p = 0.0003). Compared to children born of Christian mothers, children born to minority non-Christian mothers had higher odds of being zero-dose (AOR: 6.55, 95% CI: 1.04–41.25, p = 0.0453). Children born to fathers who are immigrants were more likely to be zero-dose children than Cameroonians (AOR: 2.60, 95% CI = 0.65–10.35, p = 0.0016). Younger children were likely to be unvaccinated compared to older peers (AOR: 0.90, 95% CI: 0.82–1.00, p = 0.0401). Conclusions: In the spirit of “leaving no child behind,” the study highlights the need to develop context-specific approaches that consider minority religious groups, immigrants, and younger children, including newborns, often missed during vaccination campaigns and outreaches

Background: The third round of the global pulse survey demonstrated that the abrupt and rapid progression of the COVID-19 pandemic significantly disrupted childhood immunization in many countries. Although Cameroon has reported over 120,000 COVID-19 cases, the reported national childhood vaccination coverage during the pandemic seems to have increased compared to that during the pre-COVID-19 period. Indeed, the first dose of the diphtheria, tetanus, and pertussis-containing vaccine (DTP-1) coverage increased from 85.4% in 2019 to 87.7% in 2020, and DTP-3 coverage increased from 79.5% in 2019 to 81.2% in 2020. The paucity of literature on the impact of COVID-19 on childhood vaccination in COVID-19 hotspot regions poses a challenge in developing a context-specific immunization recovery plan, hence the need to conduct this study. Methodology: We conducted a cross-sectional study using 2019 (pre-pandemic period) and 2020 (pandemic period) district childhood immunization data from the DHIS-2 database, weighted using completeness for each data entry against regional data completeness in 2020. Based on COVID-19 incidence, two hotspot regions were selected, with all districts (56/56) included in the final analysis. The Chi-square test was used to compare DTP-1 and DTP-3 coverage during the pre-pandemic and pandemic periods. Results: In the two hotspot regions, 8247 children missed DTP-1, and 12,896 children did not receive DTP-3 vaccines in the pandemic period compared to the results from the pre-pandemic period. Indeed, there was a significant drop in DTP-1 and DTP-3 coverage of 0.8% (p = 0.0002) and 3.1% (p = 0.0003), respectively, in the Littoral Region. Moreover, the Centre Region reported a 5.7% (p < 0.0001) and 7.6% (p < 0.0001) drop in DTP-1 and DTP-3 coverage, respectively. Most districts in the hotspot regions reported a decline in childhood immunization access (62.5%) and utilization (71.4%). Indeed, in the Littoral Region, 46% (11/24) and 58% (14/24) of districts experienced decreased vaccination access and utilization, respectively. Meanwhile, 75% (24/32) and 81% (26/32) of districts in the Centre Region experienced a drop in vaccination access and utilization, respectively. Conclusion: This study reported a situation where the national immunization indicators mask the impact of COVID-19 on childhood immunization in heavily hit regions. Therefore, this study presents valuable information for ensuring continuous vaccination service delivery during public health emergencies. The findings could also contribute to developing an immunization recovery plan and informing policy on future pandemic preparedness and response.

Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.