Peter Van Den Steen

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Patients with obstructive airway diseases (OAD), like chronic obstructive pulmonary disease (COPD) and asthma, may be at increased risk of pertussis infection. Pertussis may also trigger COPD and asthma exacerbations. Vaccination against pertussis could help protect OAD patients from the additional burden of pertussis, but there may be hesitancy related to vaccine safety and immunogenicity in such patients. We performed a meta-analysis on 5 clinical trials in adults receiving reduced-antigen tetanus-diphtheria-acellular pertussis vaccine (Tdap, Boostrix, GSK), from which we selected participants on active OAD treatment. We compared immunogenicity and reactogenicity outcomes of the meta-analysis with data from the overall populations of Tdap-vaccinated adults from 6 Tdap trials (including the 5 in the meta-analysis). The meta-analysis comprised 222 adults on active standard OAD treatment. One month post-Tdap, 89.0% and 97.2% of these adults, respectively, achieved seroprotective anti-diphtheria and anti-tetanus antibody concentrations; 78.3%–96.1% showed booster responses across the 3 pertussis antigens. These rates were consistent with those in the comparator population. The most frequently reported solicited local and systemic adverse events within 4 days post-Tdap were injection site pain (47.7%) and fatigue (19.3%), with low rates of grade 3 intensity (0.9% and 2.8%). This was consistent with Tdap reactogenicity in the comparator population. Evaluation of unsolicited and serious adverse events within 1 month post-Tdap did not identify safety concerns. In conclusion, Tdap was immunogenic and well tolerated in adults under active standard OAD treatment, with immunogenicity and safety profiles consistent with those in a comparator population representing the general adult population. Whooping cough is a very contagious respiratory disease that is most dangerous for young babies but can affect people of all ages. People with chronic lung diseases like asthma or chronic obstructive pulmonary disease (COPD) may be more likely to get ill and suffer from complications from whooping cough. Vaccination against whooping cough is an important way to help protect these people. However, some doctors may hesitate to vaccinate patients because they may worry that vaccination could worsen asthma or COPD symptoms or that drugs taken by these patients could make vaccines work less well. We therefore looked at the immunogenicity and safety of a whooping cough vaccine (Boostrix, GSK) in adults treated for chronic lung diseases like asthma or COPD. We analyzed data from 5 previous clinical studies and specifically selected data from patients taking standard medication for chronic lung diseases in these studies. We found that the immune response to whooping cough vaccination in these patients was comparable to that in a comparator group representative of the general adult population receiving Boostrix. The vaccine was as well tolerated in patients with chronic lung diseases as in the general adult population. Our results suggest that the whooping cough vaccine Boostrix can be safely given to adults taking standard medication for chronic lung diseases to help prevent severe illness and complications from whooping cough.

Pertussis is underdiagnosed and underreported in adults and patients with underlying conditions. Patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of severe pertussis. Understanding the true prevalence of pertussis infections in such patients is important. We therefore evaluated the seroprevalence of anti-pertussis toxin (PT) antibodies in a cohort of 40–85-year-old patients diagnosed with moderate, severe or very severe COPD enrolled (between June 2011 and June 2012) in the prospective, observational “Acute Exacerbation and Respiratory InfectionS in COPD” (AERIS; NCT01360398) study, conducted in England. Serum anti-PT antibodies were measured in 104 patients using an enzyme-linked immunosorbent assay on samples collected 12 months (M12) and 24 months (M24) after enrollment. Overall, 14/104 (13.5%) patients had anti-PT concentrations ≥50 IU/mL at M12 or M24, indicative of exposure to Bordetella pertussis during the preceding 2–3 years. Of these, 6/104 (5.8%) had anti-PT ≥70 IU/mL, of whom 3/104 (2.9%) had anti-PT ≥120 IU/mL, indicative of exposure within 12 and 6 months, respectively. These results show a high circulation of B. pertussis in 40–85-year-old patients with moderate, severe or very severe COPD in England between 2012 and 2014, and call for enhanced immunization to prevent pertussis infections in such patients.

As vaccine-induced immunity and protection following natural pertussis infection wane over time, adults and adolescents may develop pertussis and become transmitters to unprotected infants. In Russia, diphtheria and tetanus but not pertussis-containing vaccines are registered for older children, adolescents, or adults. The reduced-antigen-content diphtheria toxoid, tetanus toxoid, and acellular pertussis (dTpa) vaccine (Boostrix, GSK) was developed for booster vaccination of children ≥4 years of age, adolescents, and adults. A phase III, open-label, non-randomized study was performed in eight centers in Russia between January and July 2018. The objective of this study was to assess immunogenicity, reactogenicity and safety of a single dose of dTpa vaccine in healthy Russian participants ≥4 years of age (age categories 4–9 years, 10–17 years, 18–64 years, and ≥65 years). At 1 month post-booster vaccination, across all age groups, >99.0% of participants were seroprotected against diphtheria and tetanus and >96.0% of participants were seropositive for anti-pertussis antibodies. For all antibodies across all age groups, antibody GMCs increased from pre- to 1 month post-booster vaccination and booster responses to diphtheria (in 71.5% of participants), tetanus (85.3%), and pertussis antigens (≥85.6%) were observed. One serious adverse event that was not causally related to the study vaccine was reported. No fatal cases were reported throughout the study period. In conclusion, administration of the dTpa vaccine as a booster dose in healthy Russian participants induced a robust immune response to all vaccine antigens and was generally well tolerated across all age groups.

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ). Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment. At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4–97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3–99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant. As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.