Heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination against SARS-CoV-2 infection: 1-year follow-up of a phase 1/2 open-label trial.

BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds. CONCLUSION: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. CLINICAL TRIALS REGISTRATION: NCT05109559.

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.

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.

Adhesive evaluation of three types of resilient denture liners bonded to heat-polymerized, autopolymerized, or CAD-CAM acrylic resin denture bases.

STATEMENT OF PROBLEM: Levels of bond strength between different types of resilient denture liner materials bonded to different denture base acrylic resins, CAD-CAM acrylic resins in particular, have not been well reported. PURPOSE: The purpose of this in vitro study was to measure the tensile bond strength and durability of various combinations of 3 different resilient denture liners bonded to 3 different poly(methyl methacrylate) denture base materials. MATERIAL AND METHODS: The tensile bond strength of 3 resilient denture liners, namely Ufi Gel SC, Silagum-Comfort, and Vertex Soft, combined with heat-polymerized (Vertex Rapid Simplified), autopolymerized (Vertex Self-Curing), and computer-aided design and computer-aided manufacturing (CAD-CAM) (IvoBase CAD) denture base resins were tested by using a universal testing machine (total N=138). Half of the specimens were thermocycled between 5°C and 55°C for 1500 cycles before testing. After testing, modes of failure and interface surfaces were examined using light microscopy and scanning electron microscopy, respectively. Thermogravimetric analysis was carried out to analyze the differences in content between the 3 different denture base acrylic resins. RESULTS: The mean tensile bond strength values ranged from 0.36 ±0.1 MPa to 1.51 ±0.46 MPa. CAD-CAM denture base materials showed the lowest range of bond strength when coupled to resilient denture liners (0.36 to 0.42 MPa). No statistically significant differences (P=.74) were found in bond strength between the thermocycled (0.71 ±0.23 MPa) and non-thermocycled groups (0.74 ±0.21 MPa). Silicone-based resilient denture liners exhibited the highest tensile strength with each type of denture resin. All 3 types of failure modes (adhesive, cohesive, and mixed modes) were observed. CONCLUSIONS: Silicone-based resilient denture liners produced the highest tensile bond strength to all denture bases tested. Resilient denture liners bonded to CAD-CAM denture bases produced the weakest tensile bond strengths. Thermocycling did not produce statistically significant differences in tensile bond strength of the resilient denture liners to the denture base resins.