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. 2024 Aug 14;27(9):110728.
doi: 10.1016/j.isci.2024.110728. eCollection 2024 Sep 20.

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants

Javier García-Pérez  1   2 , Alberto M Borobia  3   4 , Mayte Pérez-Olmeda  2   5 , Antonio Portolés  6   7 , Luis Castaño  8 , Magdalena Campins-Artí  9 , María Jesús Bertrán  10 , Mercedes Bermejo  1   2 , José Ramón Arribas  2   4 , Andrea López  5 , Ana Ascaso-Del-Rio  6 , Eunate Arana-Arri  8 , Inmaculada Fuentes Camps  11 , Anna Vilella  10 , Almudena Cascajero  1 , María Teresa García-Morales  12 , María Castillo de la Osa  5 , Carla Pérez Ingidua  6 , David Lora  12   13   14 , Paloma Jiménez-Santana  1 , Silvia Pino-Rosa  5 , Agustín Gómez de la Cámara  13   14 , Erick De La Torre-Tarazona  1   2 , Esther Calonge  2   5 , Raquel Cruces  1 , Cristóbal Belda-Iniesta  15 , José Alcamí  1   2 , Jesús Frías  3 , Antonio J Carcas  3 , Francisco Díez-Fuertes  1   2 ; CombiVacS Study Group
Collaborators, Affiliations

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants

Javier García-Pérez et al. iScience. .

Abstract

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Keywords: Immune response; Immunology.

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Conflict of interest statement

J.A. has received fees for educational programs from Gilead, MSD, GSK and Janssen outside of the submitted work. M.C.-A. has participated in advisory boards and has received research funding from GSK, Sanofi Pasteur, Pfizer, Novavax, and Janssen. C.B.-I. is the deputy general manager of the Instituto de Salud Carlos III. J.R.A. has received fees from Janssen, outside of the submitted work. A.M.B. is principal investigator of clinical trials sponsored by GlaxoSmithKline, Daiichi-Sankyo, Janssen, and Farmalider, outside of the submitted work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow chart showing the distribution of the patients included in the study
Figure 2
Figure 2
Humoral immune response against SARS-CoV-2 spike after a third vaccine dose (A–D) Total anti-RBD immunoglobulins (A) and pseudotyped neutralization assay against the ancestral SARS-CoV-2 variant G614 (B), and variants of concern Delta (C) and BA.1 sublineage of Omicron (D). Left panels in A, B, C, and D show the results for N- subjects whereas right panels show the results for N+ participants. Levels of immunoglobulins are reported in BAU/ml and neutralizing activity in neutralizing titer 50 (NT50). All measures were summarized as geometric mean and 95% confidence interval. Ns: p > 0.05; ∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001. See also Tables S1–S10.
Figure 3
Figure 3
Effect of breakthrough infections in the immunogenicity of the third vaccine dose (Group A represent the results of participants with asymptomatic breakthrough infection (defined as any positive sample to SARS-CoV-2 nucleocapsid IgG during the study along with a negative sample at day 0). Group B represent participants asymptomatically infected before the third dose (defined as subjects with a positive sample to anti-nucleocapsid IgG at day 0). Group C represent participants who remained Nc- throughput the study period. Levels of immunoglobulins are reported in BAU/ml and neutralizing activity in neutralizing titer 50 (NT50). Data are represented as median and interquartile range. Ns: p > 0.05; ∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001.
Figure 4
Figure 4
Neutralizing capacity to different SARS-CoV-2 variants at day 180 after the third dose (A and B) NT50 in pseudovirus neutralization assay against SARS-CoV-2 variants G614, Delta, and BA.1, BA.4/BA.5, BQ.1.1, XBB.1.5/XBB.1.9, BA.2.86, and JN.1 Omicron sublineages in N- (A) and N+ (B) participants. NT50 were summarized as geometric mean and 95% confidence interval. Ns: p > 0.05; ∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001. See also Tables S11–S16.
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