COVID-19 vaccine booster induces a strong CD8+ T cell response against Omicron variant epitopes in HLA-A*02:01+ individuals

The >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster.

Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2–4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2–4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.

Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.

Neutralizing potency of COVID-19 vaccines against the SARS-CoV-2 Omicron (B.1.1.529) variant

Background: We carried out a literature search for summarizing currently published evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant neutralizing properties of serum or plasma collected from recipients of coronavirus disease 2019 (COVID-19) vaccines.Methods: An electronic search was conducted in Medline and Scopus, using the keywords “vaccine” AND “Omicron” OR “B.1.1.529” AND “SARS-CoV-2” AND “neutralization” OR “antibodies”, with no language or date limits (i.e., up to December 27, 2021). Studies with complete information on neutralization properties of COVID-19 vaccines against the Omicron variant, with or without the adjunctive effects of booster vaccine doses, were included.Results: Our final analysis included 10 published studies. In all, decreased neutralisation of SARS-CoV-2 Omicron B.1.1.529 variant was evidenced in post-vaccination samples, ranging between -4.3 folds to absence of neutralization compared to an ancestral SARS-CoV-2 strain. In all studies the COVID-19 vaccine booster dose was effective to elicit sustained enhancement of SARS-CoV-2 Omicron B.1.1.529 neutralisation, with such increase being comprised between 10-42 folds compared to the pre-booster period.Conclusion: Vaccine boosters seem strongly advisable for limiting the risk of SARS-CoV-2 Omicron (B.1.1.529) breakthrough infections.

Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases—An Interim Report from a Danish Prospective Cohort Study

Background/Purpose: In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more SARS-CoV-2 vaccine efficacy data to inform healthcare providers on the potential need for a booster vaccine. We established the ‘Detection of SARS-CoV-2 antibodies in Danish Inflammatory Rheumatic Outpatients’ study (DECODIR) in March 2021 in order to assess and compare the immunoglobulin G (IgG response) of the SARS-CoV-2 BNT162b2 vaccine (Pfizer, Groton, CT, USA/BioNTech, Mainz, Germany) and mRNA-1273 vaccine (Moderna, Cambridge, MA, USA) administered as part of the national vaccine roll out in patients with RMDs, irrespective of treatment. Patients’ SARS-CoV-2 IgG level was used as proxy to determine vaccination response. Methods: The study is a longitudinal prospective cohort study in which the SARS-CoV-2 antibody response was measured and compared at baseline and at six weeks following vaccination. The study population consisted of patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA), or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg. Bloods, patient reported outcome measurements (PROMS), clinical data, and treatment information (cs/bcs/bDMARD) were collected at baseline/6 weeks and documented in the Danish DANBIO registry. Commercially available antibody tests (ThermoFisher, Waltham, MA, USA) were used, and SARS-CoV-2 IgG levels were reported in EliA U/mL. Sufficient IgG response was defined as ≥10 EliA U/mL (manufacturers cut-off). Associations between antibody response, age, gender, disease (RA/PsA/SpA), no treatment or cs/bDMARD treatment, and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR), and bootstrapped 95% confidence interval (CI) of the median. Results: A total of 243 patients were included. We observed a significant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 34.5 EliA U/mL at 6 weeks). Seventy-two patients (32%) had an insufficient IgG response. The median IgG level in patients treated with cs/bcs/bDMARD combination therapy was significantly lower compared to patients without any DMARD treatment (12 EliA U/mL vs. 92 EilA U/mL (p < 0.01)). Conclusion: Patients treated with a combination of cs/bcs/bDMARD are at significantly higher risk of an inadequate response to SARS-CoV-2 vaccines as measured by IgG level compared to patients without DMARD treatment. IgG SARS-CoV-2 are only part of the immune response, and further data are urgently needed. At present, our results may inform healthcare providers and policy makers on the decision for the need of a booster vaccine in this particular patient group.

Three doses of the BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 B.1.1.529 (Omicron) variant of concern

We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in healthy individuals pre-infected or not with SARS-CoV-2 and immunized with three doses of the BNT162b2 vaccine. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.

Willingness to Take the Booster Vaccine in a Nationally Representative Sample of Danes

We estimate the willingness to taking the booster dose in a representative sample of Danes. We estimate an overall willingness in the adult Danish population of 85.5 percent and a willingness of 94.7 percent among primary vaccine takers. We, moreover, show that these percentages will be significantly lower among younger populations as well as among groups who do not see COVID-19 as a threat towards society and who do not perceive the advice of the health authorities as effective against disease spread.

Neutralization and Stability of SARS-CoV-2 Omicron Variant

The SARS-CoV-2 B.1.1.529/Omicron variant was first characterized in South Africa and was swiftly designated a variant of concern. Of great concern is its high number of mutations, including 30-40 mutations in the virus spike (S) protein compared to 7-10 for other variants. Some of these mutations have been shown to enhance escape from vaccine-induced immunity, while others remain uncharacterized. Additionally, reports of increasing frequencies of the Omicron variant may indicate a higher rate of transmission compared to other variants. However, the transmissibility of Omicron and its degree of resistance to vaccine-induced immunity remain unclear. Here we show that Omicron exhibits significant immune evasion compared to other variants, but antibody neutralization is largely restored by mRNA vaccine booster doses. Additionally, the Omicron spike exhibits reduced receptor binding, cell-cell fusion, S1 subunit shedding, but increased cell-to-cell transmission, and homology modeling indicates a more stable closed S structure. These findings suggest dual immune evasion strategies for Omicron, due to altered epitopes and reduced exposure of the S receptor binding domain, coupled with enhanced transmissibility due to enhanced S protein stability. These results highlight the importance of booster vaccine doses for maintaining protection against the Omicron variant, and provide mechanistic insight into the altered functionality of the Omicron spike protein.

Predictors of uncertainty and unwillingness to receive the COVID-19 booster vaccine in a sample of 22,139 fully vaccinated adults in the UK

Summary Background The continued success of the COVID-19 vaccination programme in the UK will depend on widespread uptake of booster vaccines. However, there is evidence of hesitancy and unwillingness to receive the booster vaccine, even in fully vaccinated adults. Identifying factors associated with COVID-19 booster vaccine intentions specifically in this population is therefore critical. Methods We used data from 22,139 fully vaccinated adults who took part in the UCL COVID-19 Social Study. Multinomial logistic regression examined longitudinal predictors of uncertainty and unwillingness (versus willingness) to receive a COVID-19 booster vaccine (measured 22 November 2021 to 6 December 2021), including (i) socio-demographic factors, (ii) COVID-19 related factors (e.g., having been infected with COVID-19), and (iii) initial intent to receive a COVID-19 vaccine in the four months following the announcement in the UK that the vaccines had been approved (2 December 2020 to 31 March 2021). Findings 4% of the sample reported that they were uncertain about receiving a COVID-19 booster vaccine, and a further 4% unwilling. Initial uncertainty and unwillingness to accept the first COVID-19 vaccine in 2020-21 were each associated with over five times the risk of being uncertain about and unwilling to accept a booster vaccine. Healthy adults (those without a pre-existing physical health condition) were also more likely to be uncertain or unwilling to receive a booster vaccine. In addition, low levels of current stress about catching or becoming seriously ill from COVID-19, consistently low compliance with COVID-19 government guidelines during periods of strict restrictions (e.g., lockdowns), lower levels of educational qualification, lower socio-economic position and age below 45 years were all associated with uncertainty and unwillingness. Interpretation Our findings highlight that there are a range of factors that predict booster intentions, with the strongest predictor being previous uncertainty and unwillingness. Two other concerning patterns also emerged from our results. First, administration of booster vaccinations may increase social inequalities in experiences of COVID-19 as adults from lower socio-economic backgrounds are also most likely to be uncertain or unwilling to accept a booster vaccine as well as most likely to be seriously affected by the virus. Second, some of those most likely to spread COVID-19 (i.e., those with poor compliance with guidelines) are most likely to be uncertain and unwilling. Public health messaging should be tailored specifically to these groups.