COVID-19: immune response and systems vaccinology

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

In the current reporting period we published three COVID-19 studies, one on the limited cross-variant immune response from the Omicron BA.2 strain in nave patients (PMID: 36267551), on the vaccination of patients with Stills disease (PMID: 35532082) and the effect of vaccination of CLL leukemia patients (PMID: 36630562). Immune responses in COVID-19 patients infected with SARS-CoV-2 variants and the effects of prior vaccination SARS-CoV-2 infection ranges from asymptomatic to severe with lingering symptomatology in some. When we initiated our studies in the early days of the pandemic, the immune response and prevalence of unrecognized ongoing inflammation to SARS-CoV-2 was not understood. We addressed this question and determined no lingering immunological gene signatures in asymptomatic individuals from one of the original super spreading events in Europe. As the pandemic progressed, new SARS-CoV-2 variants appeared and there was a need to understand how the immune system responds. Specifically, variants with the E484K spike mutation within the receptor binding domain (RBD), were of particular concern because it enhances escape from neutralizing antibody inhibition in vitro and may be linked with reduced vaccination efficacy. We investigated the immune response to variants carrying this escape mutation and identified a specific gene signature pointing to the preferential activation of the JAK-STA signaling pathway. We also investigated the impact of prior COVID-19 vaccination (BNT162b2) on disease course and found a reduced inflammatory response in patients infected with different variants, including Alpha and Beta. More recently we investigated the impact of omicron variants (PMID: 36267551). The Omicron variant of SARS-CoV-2 is currently the most prevalent and has produced various sublineages. We have investigated how prior exposure to SARS-CoV-2 affects the immune response to different Omicron sublineages, specifically BA.1 and BA.2. Our study reveals that individuals with no history of COVID-19 exhibit a weaker immune response when infected with the BA.2 sublineage compared to BA.1. The blood samples from individuals with no prior exposure do not show effective neutralization of the virus. However, people who had experienced COVID-19 before exhibit stronger antibody levels and neutralizing activity against both BA.1 and BA.2. Additionally, the analysis of immune cells' gene expression demonstrates distinct immune responses and antibody production patterns between BA.1 and BA.2 patients. Overall, the immune response to Omicron variant, especially BA.2, is significantly influenced by individuals' previous infection history. Systems vaccinology of mRNA and vector-based vaccines in healthy individuals and patients with immunological disorders In December 2020, the U.S. Food and Drug Administration issued the first emergency use authorization (EUA) for a vaccine for the prevention of COVID-19 caused by SARS-CoV-2. There was an urgent need to understand the immune response mounted in different population groups, young versus old and the response of individuals that had been previously infected. Equally, and maybe even more critical, is an understanding of the immune response in immunocompromised individuals, such as cancer and organ transplant patients. For this, we initiated studies with partners in Austria, Italy, Germany and South Korea. Adult-onset Stills disease (AOSD) patients are a group that might experience disease flare due to vaccination, including COVID-19 vaccination. Limited information exists about the effectiveness of COVID-19 vaccination in this population. The decision to vaccinate these patients involves balancing safety and efficacy. Previous reports have indicated that AOSD patients can have disease flare after COVID-19 vaccination, but no study has investigated their immune transcriptional response and antibody production. Our study (PMID: 35532082) examines a 58-year-old male with AOSD who experienced a mild flare after the second dose of the BNT162b2 vaccine. The research evaluates the patient's clinical progression, immune transcriptional response, and antibody levels, including neutralization activity, following vaccination. We reported an elevated immune response and high anti-Omicron-spike neutralizing activity in adult-onset Stills disease patient immunized with BNT162b2 (PMID: 35532082). Immune response of leukemia patients to COVID-19 vaccination Patients with chronic lymphocytic leukemia (CLL) undergoing treatment with B-cell pathway inhibitors and anti-CD20 antibodies often have low immune responses to SARS-CoV-2 vaccination. To understand this, we examined 15 CLL/small lymphocytic lymphoma patients who received heterologous BNT162b2/ChAdOx1 vaccination (PMID: 36630562). After two doses, the antibody response rate was 40%, rising to 53% after a booster dose. Patients on Bruton tyrosine kinase inhibitor (BTKi) and venetoclax anti-CD20 antibody within 12 months of vaccination showed weaker responses compared to those on BTKi alone. T-cell responses were robust, with a 2-dose-T-cell response rate of 80%, increasing to 93% with the booster. Transcriptional analysis revealed rapid interferon-mediated signaling activation, unrelated to antibody response magnitude. Higher counts of IGHV genes were linked to improved B-cell recovery and better antibody response. T-cell responses seemed unaffected by treatment status, while better antibody responses were associated with BTKi treatment and B-cell recovery. Boosting was especially effective when the patients' immune status improved due to CLL treatment.