Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19

Abstract

IMPORTANCE Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. OBJECTIVE To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. DESIGN, SETTING, AND PARTICIPANTS Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. INTERVENTIONS Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 10 10 viral particles or 1 × 10 11 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). MAIN OUTCOMES AND MEASURES Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. RESULTS Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. CONCLUSION AND RELEVANCE In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

Comparison of vaccine-induced thrombotic events between ChAdOx1 nCoV-19 and Ad26.COV.2.S vaccines

“…From the findings of our study, it can be inferred that CVT events after the Ad26.COV.2.S vaccine, even with a seemingly adverse radiologic profile, has a milder, more insidious clinical course. This could be due to the differential immunogenic profiles of ChAdOx1 nCoV-19 and Ad26.COV.2.S vaccines in stimulating interferon-gamma levels, which is a known mediator in diffuse intravascular coagulation [ [8] , [9] , [10] ].…”

Broad T Cell Targeting of Structural Proteins After SARS-CoV-2 Infection: High Throughput Assessment of T Cell Reactivity Using an Automated Interferon Gamma Release Assay

“…As fundamental immunology teaches that antibody responses cannot be generated without a (T) cellular helper response, unsurprisingly, specific T cell responses were found in convalescent patients (5). Along these lines, a growing body of evidence has also recognized the existence and importance of cellular responses to SARS-CoV-2 infection in the clearance and later protection from reinfections (6). By nature, such responses are less convenient to measure and unfortunately there are no high throughput methods available to quantify SARS-CoV-2 specific T cell responses in patients.…”

SARS-CoV-2 vaccines: a triumph of science and collaboration

“…It will also be important to determine if the rate of decline in antibody titers is influenced by age, sex, race/ethnicity, and/or medical comorbidities. In addition to antibody response, CD4 + and CD8 + T cell responses have been detected in vaccine recipients (27)(28)(29), and long-term follow-up will clarify the role of cellular immunity in durability of protection.…”