2/1—SARS-CoV-2 evolution and vaccines: cause for concern?
SARS-CoV-2 evolution and vaccines: cause for concern?
A number of vaccines are already licenced or progressing through phase 3 trials. Most use a recombinant spike glycoprotein: either mRNA based (the Moderna and Pfizer–BioNTech vaccines), via an adenovirus vector (the Oxford–AstraZeneca, CanSino, and Johnson & Johnson vaccines), or via injection of the protein itself (the Novavax vaccine). Only data on influenza might suggest that evolution in SARS-CoV-2 could eventually lead to a less efficacious vaccine. However, the length of the spike protein used by licensed vaccines is relatively short (∼1270 amino acids), and one preprint paper has indicated that the natural antibody response to infection (and presumably also to a spike protein-based vaccine) is concentrated in just two sections of the protein: the N-terminal domain (NTD) and receptor-binding domain (RBD). Given that the antibody response to the spike protein is so focused, could mutations in these restricted sequences lead to a less efficacious vaccine, if the human immune response is specific to the vaccine sequence? When a virus is grown under the selective pressure of a single monoclonal antibody that targets a single epitope on a viral protein, mutations in that protein sequence will lead to the loss of neutralisation, and the generation of escape mutants. This sequence of events has been shown in the laboratory for polio, measles, and respiratory syncytial virus, and in 2020 for SARS-CoV-2.
The case for No-COVID
There are three elements to their plan, based on the twin objectives of No-COVID and the creation of virus-free green zones. First, a rapid reduction in numbers of infections to zero. Second, avoidance of further virus transmission or reintroduction through rigorous test, trace, and isolate systems, together with local travel restrictions. Third, rapid outbreak management if new cases of COVID-19 occur sporadically. Experience from several east Asian countries shows that complete elimination causes the least harm to society. Every infection is one too many. The German proposal recommends a regional focus—when the incidence of infection in an area falls to zero, the region should be declared a green zone. Strict protective contact and travel restrictions should be imposed around this zone, with robust test, trace, and isolate protocols.
Last-Mile Logistics of Covid Vaccination — The Role of Health Care Organizations
About one third of U.S. “customers” are unsure that they want the product and are worried that vaccination might be made mandatory. Clinicians have a critical role in addressing vaccine reluctance, in part because of lack of trust in alternative messengers. The second task is managing demand and immunizing people who are ready to be vaccinated. Health care organizations got a taste of the complexity of this task when they began vaccinating employees. In this relatively small population with whom interactions should be reasonably straightforward, organizations had to address the same issues they will face on a much larger scale in vaccinating the public, including communication, prioritization, and management of the vaccinations themselves.
Lessons in antiviral immunity
The adaptive branch of the immune system can kill virally infected cells and generate protective immune memory, which is the basis of vaccination strategies. Both T cell and B cell responses are important in controlling viruses and the development of immunity. However, the COVID-19 pandemic is revealing widely varying immune responses and diverse clinical outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising questions about how antiviral responses are orchestrated, factors that influence the longevity of immunological memory, and approaches that mediate robust protection from viral infections.
Insights from SARS-CoV-2 sequences
Adaptation is a particular concern because SARS-CoV-2 only recently spilled over into humans and thus may still adapt to its new host through substitutions that facilitate its spread. One emerging variant that has been implicated as being more transmissible is 614G, which replaces aspartic acid (D ) with glycine (G) at amino acid site 614 in the cellular entry (spike) protein of SARS-CoV-2. This variant likely arose in China in January 2020 and has since become dominant worldwide. More recently, a new SARS-CoV-2 lineage, B.1.1.7, has rapidly spread from southeast England around the globe, and early analyses indicate that it has a substantial fitness advantage over other currently circulating lineages.
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