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. 2024 Oct 31;9(1):209.
doi: 10.1038/s41541-024-01003-x.

Safety, efficacy and immunogenicity of aerosolized Ad5-nCoV COVID-19 vaccine in a non-inferiority randomized controlled trial

Chun K Chew #  1 , Ruijie Wang #  2 , Sunita Bavanandan  3 , Norliza Zainudin  4 , Xiaoyuan Zhao  2 , Sumeyya Ahmed  2 , Damenthi Nair  5 , Lihua Hou  6 , Rosnawati Yahya  3 , Shereen S Ch'ng  4 , Lai H Pang  5 , Azrini Abdul Aziz  3 , Haitao Huang  2 , Reena Rajasuriar  7 , Shipo Wu  6 , Zhe Zhang  6 , Xuewen Wang  8 , Geok Y Chun  1 , Aisyah Mohd Norzi  5 , Kit Y Cheah  5 , Yi L Lee  5 , Wan H Wan Mohamad  3 , Mohamad R Mohd Din  3 , Wan M R Wan Ahmad Kamil  3 , Min H Tan  3 , Xiaoyu Xu  9 , Lina Wang  2 , Meixu Yan  2 , Yusi Liu  2 , Voon K Chin  2 , Jau S Teo  10 , Teck O Lim  11 , Tao Zhu  2 , Jinbo Gou  12 , Sharon S M Ng  13
Affiliations

Safety, efficacy and immunogenicity of aerosolized Ad5-nCoV COVID-19 vaccine in a non-inferiority randomized controlled trial

Chun K Chew et al. NPJ Vaccines. .

Abstract

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

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Conflict of interest statement

T.Z., J.G., R. W., S.A, H.H., X.Y.Z, L.W., M.Y., Y.L. and V.K.C. reported being employed by CanSino Biologics Inc. which manufacture the study vaccine, during the conduct of the study and outside the submitted work. J.G. and T.Z. reported holding stock in CanSino Biologics Inc. T.O.L. reported serving as a paid senior scientific advisor to CanSino Biologics Inc. S.Ng., D.N., S.B., R.Y., N.Z., S.S.C., A.A.A., C.C.K. and, L.H.P. reported receiving research grants via Clinical Research Malaysia (CRM) through a contract with CanSino Biologics Inc. during the conduct of the study and outside the submitted work. R.R. and X.W. received financial support from CanSino Biologics Inc. for contracted work outside the submitted work. X.X.X and J.S.T. received financial support from CanSino Biologics Inc. for contracted work outside the submitted work. G.Y.C., A.M.N, K.Y.C, Y.L.L, W.H.W.M, M.R.M.D., W.M.R.W.A.K. and M.H.T. reported receiving research grants from Clinical Research Malaysia (CRM) through a contract with CanSino Biologics Inc. No other disclosures were reported.

Figures

Fig. 1
Fig. 1. Participant disposition flow chart.
BNT-IM Intramuscular tozinameran vaccine, Ad5-nCoV-IH Recombinant Covid-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation.
Fig. 2
Fig. 2. Immune responses elicited by a second booster vaccination.
Ad5-nCoV-IH Recombinant Covid-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation, BNT-IM intramuscular tozinameran vaccine, Anti-spike RBD IgG anti-spike receptor binding domain immunoglobulin G, GMC geometric mean concentration, GMT geometric mean titer, PNA pseudo neutralization assay, SIgA secretory Immunoglobulin A. a GMC of S-RBD IgG antibodies (wild-type). b GMT of Pseudovirus Neutralizing Antibodies (BA.4/5). The blue bar is Ad5-nCoV-IH group among which primary immunogenicity assessments were performed at Day 0, Day 14, and Day 28 for 270 participants, and persistent immunogenicity assessments were performed at Day 84 and Day 168 for 139 participants. The orange bar is BNT-IM group among which primary immunogenicity assessments were performed at Day 0, Day 14, and Day 28 for 268 participants, and persistent immunogenicity assessments were performed at Day 84 and Day 168 for 141 participants. c GMC of SIgA antibodies against Spike protein from BA.2.75, BA.2.75.2, and BA.4.6. The blue bar is Ad5-nCoV-IH group among which immunogenicity assessments were performed at Day 0, Day 14, Day 28, and Day 84 for 44 participants. The orange bar is BNT-IM group of which 44 participants’ immunogenicity assessments were performed at Day 0, Day 14, Day 28 and Day 84. * Indicates statistically significant differences between the Ad5-nCoV-IH group and the BNT-IM group (p < 0.05).
Fig. 3
Fig. 3. Solicited and unsolicited ADRs emerged in the 0 to 28 Days post booster vaccination (SS).
Percentage of participants experienced ADR(s). The analysis was based on the safety cohort (SS), included all randomized participants who received the booster vaccination and had at least one evaluation data available (270 participants from the Ad5-nCoV-IH group and 269 participants from the BNT-IM group). *P < 0.05, **P < 0.001.
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