ABSTRACT
Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against coronavirus disease 2019 (COVID-19). This immunity may further be shaped by cross reactivity with common cold coronaviruses. Mutations arising in S that are associated with altered intrinsic virus properties and immune escape result in the continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will be required to protect against future variants of concern, as for influenza. To offer potent protection against future variants, these second-generation vaccines may need to redirect immunity to epitopes associated with immune escape and not merely boost immunity toward conserved domains in preimmune individuals. For influenza, efficacy of repeated vaccination is hampered by original antigenic sin, an attribute of immune memory that leads to greater induction of antibodies specific to the first-encountered variant of an immunogen compared with subsequent variants. In this Review, recent findings on original antigenic sin are discussed in the context of SARS-CoV-2 evolution. Unanswered questions and future directions are highlighted, with an emphasis on the impact on disease outcome and vaccine design.
ABSTRACT
The emergence and rapid spread of SARS-CoV-2 variants may affect vaccine efficacy substantially. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early SARS-CoV-2 variants (614G, Alpha, Beta, Gamma, Zeta, Delta, and Mu) using hamster antisera obtained after primary infection. We first verified that the choice of the cell line for the neutralization assay did not affect the topology of the map substantially. Antigenic maps generated using pseudo-typed SARS-CoV-2 on the widely used VeroE6 cell line and the human airway cell line Calu-3 generated similar maps. Maps made using authentic SARS-CoV-2 on Calu-3 cells also closely resembled those generated with pseudo-typed viruses. The antigenic maps revealed a central cluster of SARS-CoV-2 variants, which grouped on the basis of mutual spike mutations. Whereas these early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape vaccine-induced antibody responses as a result of different antigenic characteristics. Thus, antigenic cartography could be used to assess antigenic properties of future SARS-CoV-2 variants of concern that emerge and to decide on the composition of novel spike-based (booster) vaccines.
ABSTRACT
Almost two years after the introduction of SARS-CoV-2, it has become clear that the virus is unlikely to disappear any time soon. It is also clear that the virus mutates, resulting in specific variants of SARS-CoV-2. The exact implications of these variants are being investigated but it is likely that they have a selective advantage over previously circulating variants. It is possible that SARS-CoV-2 will mutate in the coming years to such an extent that existing vaccines do not offer sufficient protection against hospitalizations in the general population. At present, the protection of current vaccines against infection is observed to be reduced by the emergence of variants but remains high against hospitalizations and severe disease. Booster vaccinations are currently advised for specific risk groups where the regular vaccination schedule leads to an insufficient immune response, and are being considered for people in old age where the vaccine effectiveness is lower.
ABSTRACT
Background: Patients with cancer have an increased risk of complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination is recommended, but the impact of chemotherapy and immunotherapy on immunogenicity and safety is still unclear. Methods: This prospective multicenter non-inferiority trial comprises four cohorts: individuals without cancer (A) and patients with solid tumors who were treated with immunotherapy (B), chemotherapy (C) or chemo-immunotherapy (D). Participants received two mRNA-1273 vaccinations 28 days apart. The primary endpoint was SARS-CoV-2 Spike S1-specific IgG serum antibody response, defined as >10 binding antibody units (BAU)/ml 28 days after the second vaccination. We also assessed the virus neutralizing capacity of these antibodies, SARS-CoV-2 Spike-specific interferon-gamma T cell response, and adverse events. Results: Of the 791 participants enrolled, 743 were evaluable for the primary endpoint in cohort A (n=240), B (n=131), C (n=229) and D (n=143). A SARS-CoV-2-binding antibody response was found in 100%, 99.3%, 97.4%, and 100% of the participants in cohorts A, B, C, and D, respectively. To discriminate between suboptimal and adequate responders, we defined a cut-off level at 300 BAU/ml, based on neutralizing capacity. The antibody response was considered adequate after the first vaccination in 66.0%, 37.1%, 32.5%, and 33.3% of the participants in cohorts A, B, C, and D, respectively. This raised 28 days after the second vaccination to respectively 99.6%, 93.1%, 83.8%, and 88.8% in cohorts A, B, C, and D. Spike-specific T cell responses were detected in 46.7% of suboptimal and non-responders. No new safety signals were observed. Conclusions: mRNA-1273 vaccination is safe in the patient populations studied. For each cohort, the proportion of patients with a SARS-CoV-2-binding antibody response after two vaccinations is non-inferior compared to individuals without cancer. However, a significant minority lacks an adequate response. Most patients have an antibody concentration increase after the second vaccination. Therefore, an additional booster may turn inadequate into adequate responders. Clinical trial identification: NCT04715438. Legal entity responsible for the study: University Medical Center Groningen, the Netherlands. Funding: ZonMw, The Netherlands Organisation for Health Research and Development. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
China is struggling with the outbreak of a new coronavirus that is not yet under control. What exactly is going on, what do we know and what not, and how should we proceed? This article lists the current state of affairs and discuss the international approach, as well as discussing past outbreaks, what they currently know about COVID-19, and public health preparation to control and prevent transmission of the virus in Netherlands.
ABSTRACT
AIM: To investigate the sources of infection among healthcare workers (HCWs) and patients in a teaching hospital in the Netherlands during the early stages of the coronavirus disease 2019 (COVID-19) pandemic using epidemiological and whole-genome sequencing data. METHODS: From 3rd April to 11th May 2020, 88 HCWs and 215 patients were diagnosed with COVID-19. Whole-genome sequences were obtained for 30 HCWs and 20 patients. RESULTS: Seven and 11 sequence types were identified in HCWs and patients, respectively. Cluster A was the most common sequence type, detected in 23 (77%) HCWs; of these, 14 (61%) had direct patient contact and nine (39%) had indirect patient contact. In addition, seven patients who were not hospitalized in the COVID-19 cohort isolation ward who became positive during their admission were infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cluster A. Following universal masking of all HCWs and emphasis on physical distancing during meals and breaks, no further evidence was found for patient-to-HCW or HCW-to-HCW transmission or vice versa. CONCLUSION: The finding that patients and HCWs were infected with SARS-CoV-2 cluster A suggests both HCW-to-HCW and HCW-to-patient transmission.