Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines

Abstract

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of viral Spike S1 protein encoding mRNA incorporated in a lipid nanoparticle and stabilized by polyethylene glycol (PEG). The mRNA vaccines are novel in many respects, including cellular uptake and the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences, encoding the SARS-CoV-2 Spike protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to the induction of virus-neutralizing antibodies and cytotoxic T-lymphocytes, will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. The mRNA-based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG and potential presentation in the context of CD1 will be discussed. Adenovirus vector-based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

Real Concerns over COVID-19 Variants of Concern

“…It is best that humans never face such variant, which indeed should be named the omega () variant. Accordingly, it is recommended to refrain from using the available vaccines (34,35) and only rely on the spike glycoprotein subunit 1 in a protein form (17) for vaccination of individuals with underlying morbidities, advanced age, and at serious risk.…”

mRNA COVID-19 Vaccines and Long-Lived Plasma Cells: A Complicated Relationship

“…Therefore, the vaccine spike protein must be present in the cytosol of the DCs that have captured the LNPs in the extracellular area, or from the non-immune cells, at the injection site. After exiting the endosomes, mRNA can be translated in the ribosomes and then arrives at the endoplasmic reticulum (ER), undergoes post-translational modifications [14], and can be associated with Class-I MHC molecules, and then exposed to the DC surfaces for presentation to B and TCD8 lymphocytes. Now it remains to be understood how TCD4 helper lymphocytes can be activated.…”

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

“…Thanks to its lipid structure, endocytosis of LNPs occurs and the mRNA is released into the host cell cytosol, where mRNA combines with ribosomes and begins to be translated to form metastable trimeric prefusion S protein. After translation, the S protein is shuttled through the endoplasmic reticulum and Golgi complex resulting in the presentation of the full length S protein assembled in a trimer structure at the cell membrane [ 63 ]. This membrane antigen (not in the context of major histocompatibility complex –MHC–) is the main target for B cell recognition [ 64 ].…”