![]() ![]() There are two major types of mRNA vaccines: those that use nonreplicating mRNA that simply encodes the target antigen, and those that use self-amplifying mRNA, which encodes both the antigen and viral genome replication proteins that replicate the mRNA within transfected cells. ![]() Both currently approved SARS-CoV-2 mRNA vaccines (Pfizer/BioNTech's and Moderna's) utilize the S-2P construct.Ĭompanies involved in SARS-CoV-2 mRNA vaccine development: vaccine types, vaccine administration, and status of development This latter construct is stabilized in the prefusion conformation by proline substitutions in the S2 subunit (K986P and V987P) and is believed to induce superior neutralizing antibody responses compared to its WT counterpart, as previously observed for the S protein of Middle East respiratory syndrome coronavirus (MERS-CoV) ( 10). mRNA vaccine companies have designed and produced various versions of S-encoding mRNAs ( Table 1), including the wild-type (WT) full-length S a trimerized, soluble version of RBD and, most importantly, a membrane-bound full-length construct named S-2P. The S protein has two subunits: S1, which contains the receptor binding domain (RBD) and multiple neutralizing epitopes and S2, which is responsible for viral fusion with the host cell membrane ( 9). The most widely used vaccine target is the spike (S) surface glycoprotein, which mediates viral attachment and entry via the cellular receptor angiotensin-converting enzyme 2 (ACE-2). Immune responses against several SARS-CoV-2 antigens could potentially contribute to protection from infection or viral clearance. SARS-COV-2 MRNA VACCINE PLATFORMS AND ANTIGENS This clear and rapid success has thrust mRNA vaccines into the spotlight in both the scientific community and the general public.Īt this critical juncture, we review the SARS-CoV-2 mRNA vaccine field, discussing preclinical and clinical data, mechanisms of immune activation (known and unknown), and perspectives on the bright future ahead for this revolutionary vaccine modality. Since then, the immunization of hundreds of millions of people with these vaccines has significantly contributed to the mitigation of COVID-19 morbidity and mortality in countries with robust vaccination programs. Both vaccines have received widespread approval for human use, and administration of these regimens started in December 2020. A second advantage, besides the ease of design and production, is that the SARS-CoV-2 mRNA vaccines generated by Moderna and Pfizer/BioNTech have shown very high efficacy (∼90% at ≤6 months of follow-up) in phase III clinical trials and in the general population ( 5– 8). This feature of mRNA vaccines makes them particularly suitable for tackling rapidly emerging outbreaks. designed and produced a good manufacturing practice (GMP)-quality SARS-CoV-2 mRNA vaccine (mRNA-1273) for human trials only 42 days after obtaining the nucleotide sequence of the target antigen. One of the most critical advantages of this vaccine type over traditional platforms is that its synthetic nature and sequence-independent manufacturing allow extremely fast and flexible vaccine design and production ( 4). Messenger RNA (mRNA) vaccines represent a new vaccine class that has proven to be highly effective in preclinical and clinical studies against infectious diseases ( 3). Several vaccines have already received approval for human use, and many more are in late-stage clinical development ( 2). Due to tight cooperation among governments, regulatory agencies, and manufacturers, vaccine development proceeded with historically unprecedented speed ( 1). Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be crucial for ending the ongoing serious pandemic of coronavirus disease 2019 (COVID-19). This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. ![]() This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. ![]() Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ![]()
0 Comments
Leave a Reply. |