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Clinical Trial
. 2023 Jul 19;41(32):4648-4657.
doi: 10.1016/j.vaccine.2023.06.043. Epub 2023 Jun 15.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial

Sant Muangnoicharoen  1 , Rakpong Wiangcharoen  2 , Sira Nanthapisal  3 , Supitcha Kamolratakul  1 , Saranath Lawpoolsri  4 , Anan Jongkaewwattana  5 , Arunee Thitithanyanont  6 , Viravarn Luvira  1 , Pailinrut Chinwangso  7 , Narumon Thanthamnu  1 , Narisara Chantratita  8 , Jacqueline Kyungah Lim  9 , T Anh Wartel  9 , Jean-Louis Excler  9 , Martin F Ryser  10 , Chloe Leong  11 , Tippi K Mak  12 , Punnee Pitisuttithum  13
Affiliations
Clinical Trial

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial

Sant Muangnoicharoen et al. Vaccine. .

Abstract

Background: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented.

Methods: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood.

Results: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups.

Conclusions: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups.

Clinical trials registration: NCT05109559.

Keywords: Ad26.COV2.S; COVID-19; Delta; Heterologous booster; Neutralizing antibodies; Omicron; SARS-CoV-2; Thailand; Variants of concern; Whole inactivated virus vaccine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.M., R.W., S.K., S.L., A.J., A.T., V.L., P.C., N.T., N.C. report no potential conflicts of interest. S.N. has received honoraria for lectures from GSK, Zuellig Pharma, Astra Zeneca, Novartis, Abbot, Sanofi, Organon and Takeda and has participated in advisory boards for GlaxoSmithKline and Takeda. J.K.L. and T.A.W. and received institutional funding from Mahidol University to support study conduct, and T.A.W. supported management of Data Safety Monitoring Board activities and meetings. J-L.E. has received funding from Mahidol University and Johnson & Johnson for study support, and is the coordinator of the study Data Safety Monitoring Board. M.F.R. is an employee of Janssen Pharmaceuticals and holds restricted stock units in the company. C.L. is an employee of Janssen Pharmaceuticals. T.K.M. has received consulting fees from Janssen Pharmaceuticals. P.P. has received funding from Mahidol University and Johnson & Johnson for study support.

Figures

Fig. 1
Fig. 1
Trial profile.
Fig. 2
Fig. 2
Solicited local and systemic adverse events during the first 7 days after study vaccination in the safety population. Ad26.COV2.S booster was given 90–240 days (Group A1; n = 360) or 45–75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Grade 1 = mild; grade 2 = moderate; grade 3 = severe; grade 4 = inability to provide basic self-care, intervention indicated to prevent permanent impairment.
Fig. 3
Fig. 3
Humoral immunogenicity. (A) Binding antibody response against SARS-CoV-2: GMC in BAU/mL of anti-S IgG measured by ELISA in the per protocol population. At baseline, GMC and 95 % CI were adjusted for age; at other visits, GMC and 95 % CI were adjusted for age and baseline log-antibody concentration. (B) Neutralizing antibody responses: GMT of NT50 measured by pNA (top panels) and mNA (bottom panels) against ancestral SARS-CoV-2 and variants of concern in a subset of the per protocol population Ad26.COV2.S booster was given 90–240 days (Group A1) or 45–75 days (Group A2) after the second BBIBP-CorV dose. BAU, binding antibody units, obtained by applying a correlation factor of 0.97 to convert the results from ELISA U/mL; ELISA, enzyme-linked immunosorbent assay; GMC, geometric mean concentration; GMT, geometric mean titer; mNA, microneutralization assay; NT50, 50 % neutralization titer; pNA, pseudovirus neutralization assay.
Fig. 4
Fig. 4
Proportion of participants with seroresponsesa to Ad26.COV2.S booster at day 28 in the per protocol population. Ad26.COV2.S booster was given 90–240 days (Group A1) or 45–75 days (Group A2) after the second BBIBP-CorV dose. ELISA, enzyme-linked immunosorbent assay; mNA, microneutralization assay; pNA; pseudovirus neutralization assay; S, spike protein of SARS-CoV-2. a Defined as a ≥ 4-fold increase from baseline at days 28 in anti-S IgG (measured by ELISA) or in 50 % neutralization seroresponses against SARS-CoV-2 pseudovirus and variants (measured by pNA and mNA). b In a subset of participants.
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