ABSTRACT
Background: Ad26.COV2.S is a single-shot vaccine that has demonstrated clinical efficacy against symptomatic COVID-19. In this study, we report the durability of immune responses in 20 rhesus macaques received single-shot Ad26.COV2.S and the immunogenicity of a booster shot at 8-10 months following the initial immunization. Methods: Animals were immunized by intramuscular route with 1011 vp (N=10) or 5x1010 vp (N=10) Ad26.COV2.S and were followed for either 230 or 315 days. Animals were then boosted with 5x1010 vp Ad26.COV2.S (N=10). Humoral immune responses including RBD-specific Ig ELISA and pseudovirus-based virus neutralization response were monitored. Circulating RBD-specific memory B cells and bone marrow plasma cells were assessed by multiparameter flow cytometry. Results: Ad26.COV2.S elicited robust and comparable RBD-specific binding and neutralizing antibody responses in animals that received the 1011 vp and 5x1010 vp doses, which peaked on days 28-56, and then showed a biphasic decay. All animals showed binding antibody responses for the duration of follow-up, and 17 of 20 animals showed neutralizing antibody responses by day 230-315. RBD-specific memory B cell response peaked on day 14-28 followed by a gradual decline, and remained detectable in 17 of 20 animals by day 230-315. On day 315 following vaccination, bone marrow RBD-specific PCs were detected in the majority of vaccinated macaques, including in all animals that received the 1011 vp dose. Following Ad26.COV2.S boost immunization, RBD-specific binding antibody responses increased 31-69 fold compared with pre-boost levels against the ancestral (WA1/2020), alpha (B.1.1.7), beta (B.1.351), kappa (B.1.617.1), and delta (B.1.617.2) SARS-CoV-2 variants. Neutralizing antibody responses increased 23-43 fold compared with pre-boost levels against the ancestral, alpha, beta, gamma (P.1), kappa, and delta SARS-CoV-2 variants. Antigen-specific memory B cell response also increased 8 fold following the boost immunization. Conclusion: Ad26.COV2.S elicited durable antibody and B cell responses, and a late boost with Ad26.COV2.S resulted in a dramatic increase in humoral immunity that were highly cross-reactive across multiple SARS-CoV-2 variants in rhesus macaques. These data contribute to our understanding of Ad26.COV2.S durability and boostability, and provide important data to inform COVID-19 vaccine boosting strategies in humans.
ABSTRACT
A 59-year-old male patient was admitted to hospital diagnosed with moderate pneumonia associated with COVID-19. Upfront treatment with hydroxychloroquine and azithromycin was started. Due to a clinical deterioration (ARDS, circulatory shock) and greatly increased inflammation markers 6 days after admission, a cytokine storm was suspected and off-label treatment with the IL6 receptor antagonist tocilizumab was initiated. Subsequently there was a dramatic rise of Ddimers indicating pulmonary intravascular coagulopathy and respiratory insufficiency worsened. After a second dose of tocilizumab was administered severe perimyocarditis with cardiac arrhythmia, hemodynamic instability and ST elevation occurred. Shortly afterwards the patient died due to multiorgan failure. From our experience, exacerbation of COVID-19 following treatment with tocilizumab cannot be ruled out. Randomized controlled studies are necessary to further investigate the efficacy, safety and patient selection criteria for tocilizumab treatment in COVID-19.