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Clinical Trial
. 2023 Dec 31;19(1):2187194.
doi: 10.1080/21645515.2023.2187194. Epub 2023 Mar 28.

Immunogenicity and safety of the non-typable Haemophilus influenzae- Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Ilaria Galgani  1 , Airi Põder  2 , Rain Jõgi  3 , Veli-Jukka Anttila  4 , Stefano Milleri  5 , Alberto M Borobia  6   7   8   9 , Odile Launay  10   11   12 , Marco Testa  1 , Daniela Casula  1 , Luca Grassano  1 , Annaelisa Tasciotti  1 , Marie Dozot  13 , Ashwani K Arora  14
Affiliations
Clinical Trial

Immunogenicity and safety of the non-typable Haemophilus influenzae- Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Ilaria Galgani et al. Hum Vaccin Immunother. .

Abstract

A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50-80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.

Keywords: AS01; Moraxella catarrhalis; adjuvant system; chronic obstructive pulmonary disease; immune response; non-inferiority; non-typable Haemophilus influenzae; recombinant zoster vaccine.

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Conflict of interest statement

IG, LG, AT, MD, and AKA are employed by GSK. MD is also married to an employee of GSK and both own shares in GSK. AKA is an inventor named on patent applications filed in the name of GSK. RJ reports personal fees from GSK, during the conduct of the study. RJ also discloses personal fees and non-financial support from GSK and Boehringer Ingelheim, and personal fees from Novartis, outside the submitted work. MT was an employee of GSK when this study was conducted and is now an employee of Janssen-Cilag S.p.A. Cologno Monzese, Italy. MT is an inventor named on patent applications filed in the name of GSK. DC was an employee of GSK when this study was conducted and is now an employee of Seqirus srl. DC is an inventor named on patent applications filed in the name of GSK. V-JA reports consulting fees from MSD and Pfizer, and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from MSD, Pfizer, Astellas, Roche, Biogen, Unimed, Astra-Zeneca, and GSK, outside the submitted work. AP and SM have nothing to disclose. OL reports payment or honoraria for educational events from MSD, Pfizer, Sanofi Pasteur, Janssen and GSK, outside the submitted work and DMSB participation from Sanofi and MSD. AMB has received advisory fees and speaker fees from Janssen and Pfizer. All authors declare no other financial and non-financial relationships and activities.

Figures

Figure 1.
Figure 1.
Plain language summary.
Figure 2.
Figure 2.
Participant disposition.
Figure 3.
Figure 3.
Non-inferiority of sequential administration of RZV and NTHi-Mcat vaccine versus NTHi-Mcat alone: GMC ratios at 1 month after the second dose of NTHi-Mcat vaccine (per-protocol set).
Figure 4.
Figure 4.
GMCs against each NTHi-Mcat vaccine antigen pre-vaccination and at 1 month after the second vaccine dose (per-protocol set).
Figure 5.
Figure 5.
Frequency of antigen-specific CD4+ T-cells expressing at least two activation markers upon in vitro stimulation with each NTHi-Mcat vaccine antigen, pre-vaccination and at 1 month after the second vaccine dose (per-protocol CMI sub-cohort).
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