Safety and immunogenicity of non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine

• Published in: Vaccine 2019-05, Vol.37 (23), p.3113-3122
• Main Authors: Van Damme, Pierre, Leroux-Roels, Geert, Vandermeulen, Corinne, De Ryck, Iris, Tasciotti, Annaelisa, Dozot, Marie, Moraschini, Luca, Testa, Marco, Arora, Ashwani Kumar
• Format: Article
• Language: English
• Subjects: Acute exacerbation; Adults; Antigens; Chronic obstructive pulmonary disease; Clinical trial; COPD; Formulations; Haemophilus influenzae; Immune response; Immune response (humoral); Immune system; Immunogenicity; Moraxella catarrhalis; Older people; Proteins; Randomization; Safety; Smoking; Streptococcus infections; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.04.041

•The combined NTHi-Mcat vaccine had an acceptable safety and reactogenicity profile.•Most reactions were mild/moderate and resolved within a few days after vaccination.•Reactogenicity was highest in the adjuvanted NTHi-Mcat vaccine groups.•The protein vaccine had good immunogenicity in older adults with a smoking history. Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are frequent pathogens in acute exacerbations of COPD. We assessed the safety, reactogenicity and immunogenicity of different investigational vaccine formulations containing surface proteins of NTHi (PD and PE-PilA) and Mcat (UspA2) in adults with smoking history ≥10 pack-years, to immunologically represent the COPD population. Participants received two doses 60 days apart in a randomised, observer-blind, placebo-controlled study (NCT02547974). In step 1, 30 healthy adults aged 18–40 years were randomised (1:1) to receive a non-adjuvanted formulation (10-10-PLAIN) or placebo. In step 2, 90 smokers/ex-smokers aged 50–70 years randomly (1:1:1) received an AS01-adjuvanted formulation containing either 10 µg of each antigen (10-10-AS01) or 10 µg of each NTHi antigen and 3.3 µg of Mcat antigen (10-3-AS01), or placebo. Incidences of solicited local adverse events (AEs) tended to be highest in the AS01-adjuvanted vaccine groups. Most solicited AEs had mild/moderate intensity. No vaccine-related serious AEs were reported. The 10-3-AS01 formulation induced the best humoral immune response against the NTHi antigens. Responses against the Mcat antigen were similar across groups, with waning immunogenicity after 30 days post-dose 2. The investigational NTHi-Mcat vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in older adults with a smoking history.