Other components of cellular immunity, such as CD8 T cells, also contribute to immune responses after SARS-CoV-2 infection or vaccination, although their role in COVID-19 infections and protection from disease is still incompletely resolved 12, 13.Ĭurrent COVID-19 vaccines present the spike protein in very different ways to the immune system, and two main categories have to be discerned. Efficient formation of such antibodies by B cells requires helper functions of CD4 T cells that are specifically stimulated by peptides derived from the same antigen in complex with MHCII molecules. The potency of these antibodies depends on high-affinity interactions with specific parts of the complex three-dimensional structure of the spike in a native conformation 10, 11. Increasing evidence indicates that neutralizing antibodies are indeed a reliable correlate of protection 5, 6, 7, 8, 9. Because of its essential functions during viral entry (receptor binding and membrane fusion), the S protein is the major target of antibodies that can potently neutralize the virus. ![]() duration of immunity, prevention of transmission, and protection against emerging virus variants) the availability of effective COVID-19 vaccines is an enormous relief and certainly a great success story already now.Īll current vaccines that are authorized for general use and for which clinical efficacy data have been published rely on the viral spike protein (S) as an immunogen, either alone or-in the case of inactivated virus vaccines-together with other viral proteins present in the viral particle (see sections below). Despite incompletely resolved questions (e.g. These vaccines are now used worldwide for mass immunization programs, and data on vaccine efficacies justify the hope that vaccination can indeed be the main instrument for preventing serious disease and death, and more generally for combating the pandemic 1, 2, 3, 4. ![]() The development of COVID-19 vaccines was extremely fast and successful, with several manufacturers having obtained market authorization for their products within the first year from the identification of the virus (SARS-CoV-2). Distinguishing characteristics and unknown features are highlighted in the context of protective antibody responses and reactogenicity of vaccines. In this article, we review the relevance of structural modifications of S in different vaccines and the different modes of antigen expression after vaccination with genetic adenovirus-vector and mRNA vaccines. They all rely on the native viral spike protein (S) of SARS-CoV-2 for inducing potently neutralizing antibodies, but the presentation of this key antigen to the immune system differs substantially between the different categories of vaccines. mRNA, adenoviral vector as well as inactivated whole-virus vaccines are now in widespread use, and a subunit vaccine is in a final stage of authorization. This enormous progress was achieved with fundamentally different vaccine technologies used in parallel. Several of them have reached market authorization and mass production, leading to their global application on a large scale. COVID-19 vaccines were developed with an unprecedented pace since the beginning of the pandemic.
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