Ad26.COV2.S priming provides a solid immunological base for mRNA-based COVID-19 booster vaccination (preprint)

A large proportion of the global population received a single dose of the Ad26.COV2.S coronavirus disease-2019 (COVID-19) vaccine as priming vaccination, which was shown to provide protection against moderate to severe COVID-19. However, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that harbor immune-evasive mutations in the spike protein led to the recommendation of booster vaccinations after Ad26.COV2.S priming. Recent studies showed that heterologous booster vaccination with an mRNA-based vaccine following Ad26.COV2.S priming leads to high antibody levels. However, how heterologous booster vaccination affects other functional aspects of the immune response remains unknown. Here, we performed immunological profiling on samples obtained from Ad26.COV2.S-vaccinated individuals before and after a homologous (Ad26.COV2.S) or heterologous (mRNA-1273 or BNT162b2) booster vaccination. Both homologous and heterologous booster vaccination increased antibodies with multiple functionalities towards ancestral SARS-CoV-2, the Delta and Omicron BA.1 variants. Especially, mRNA-based booster vaccination induced high levels of neutralizing antibodies and antibodies with various Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. In contrast, T cell responses were similar in magnitude following homologous or heterologous booster vaccination, and retained functionality towards Delta and Omicron BA.1. However, only heterologous booster vaccination with an mRNA-based vaccine led to the expansion of SARS-CoV-2-specific T cell clones, without an increase in the breadth of the T cell repertoire as assessed by T cell receptor sequencing. In conclusion, we show that Ad26.COV2.S priming vaccination provides a solid immunological base for heterologous boosting with an mRNA-based COVID-19 vaccine, increasing humoral and cellular responses targeting newly emerging variants of concern.

Impacts of the COVID-19 pandemic on future seasonal influenza epidemics (preprint)

Summary Seasonal influenza viruses typically cause annual epidemics worldwide infecting 5-15% of the human population 1 . However, during the first two years of the COVID-19 pandemic, seasonal influenza virus circulation was unprecedentedly low with very few reported infections 2 . The lack of immune stimulation to influenza viruses during this time, combined with waning antibody titres to previous influenza virus infections, could lead to increased susceptibility to influenza in the coming seasons and to larger and more severe epidemics when infection prevention measures against COVID-19 are relaxed 3,4 . Here, based on serum samples from 165 adults collected longitudinally before and during the pandemic, we show that the waning of antibody titres against seasonal influenza viruses during the first two years of the pandemic is likely to be negligible. Using historical influenza virus epidemiological data from 2003-2019, we also show that low country-level prevalence of each influenza subtype over one or more years has only small impacts on subsequent epidemic size. These results suggest that the risks posed by seasonal influenza viruses remained largely unchanged during the first two years of the COVID-19 pandemic and that the sizes of future seasonal influenza virus epidemics will likely be similar to those observed before the pandemic.

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability (preprint)

The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated neutralizing antibodies from convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 {micro}g/mL, making them the most potent human SARS-CoV-2 antibodies described to date. Mapping studies revealed that the SARS-CoV-2 spike protein contained multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as previously undefined non-RBD epitopes. In addition to providing guidance for vaccine design, these mAbs are promising candidates for treatment and prevention of COVID-19.