These Vaccines May Be Ready to Take On New COVID Variants

The vaccine will be ready by March. It will be the first revision of the vaccine since the FDA approved it in December of 2020. The FDA and other major regulators will be shown how quickly they can approve applications for vaccine revisions by the variant-specific booster.

The rapid spread of the highly transmissible Omicron variant of SARS-CoV-2 despite protection from the first generation of vaccines demonstrates the sheer unpredictability of the epidemic. As new versions of COVID-19 vaccines lose their effectiveness, producers and developers are replacing them with variant-ready vaccines and boosters. Others are focused on developing protective vaccines, while others have vaccines in development to promote T-cell responses.

The fastest time to make a vaccine is several months, lagging behind the surge of infections due to new viruses. There is a risk that providing booster shots will become a default strategy in the absence of effective multivalent vaccines that provide cross-strain protection.

The initial batches of the vaccine were expected to be available about 100 days after regulatory approval. After obtaining disappointing clinical data with its first vaccine candidate, the Tübingen, Germany-based biotech is now developing a second-generation mRNA vaccine, which is designed for improved expression of an antigen, a substance that stimulates an immune response.

Changing the sequence of plasmid DNA is the first step in the development of a variant-ready vaccine. The vaccines made by Pfizer and Moderna are based on the plismid DNA, which is designed to mimic natural counterparts and protect them from degradation.

The step from the plasmid to the messenger RNA remains the same. We would expect that a different payload would be encapsulated and delivered with our carriers with the same efficiency as the current one. It doesn't matter what you put in the package, it gets delivered to the address.

The process of changing to a new vaccine based on a different type of molecule is slower than before. Vaccines that use a virus that serves as a means to deliver a vaccine into cells also depend on cell-based production.

Several groups are aiming to develop products that induce cross-strain protection by including portions of the SARS-CoV-2 spike proteins from several different strains that are recognized by the immune system and can generate a protective response. Although the development and manufacturing timescales are longer, the unpredictable course of the Pandemic has put these options on a more realistic footing.

Helen Horton, chief research officer at London-based Touchlight, says that everyone agrees that coronaviruses isn't going anywhere soon. She says that we are seeing greater immunogenicity.

Experts anticipated the problem of immune escape variants that don't protect against vaccine during the early stages of the Pandemic. Within a year of the start of the Pandemic, effective products became available in large volumes, thanks to the almost exclusive focus of the first wave of vaccine developers. The ability of the spike protein to evade neutralizing antibody responses quickly became apparent, as it also created vulnerabilities.

The administration of vaccines and spike-protein-targeting therapeutic antibodies exerts a pressure on escape variant. The high levels of immunity seen during the first half of the year were a fleeting phenomenon. He says that it is probably no longer realistic to expect protection against disease. The existing vaccines are still effective. The death rate of older unvaccinated patients is 15 times higher than that of fully vaccineed patients, according to recently released data from Washington State's Department of Health.

T-cells and other immune cells are likely driving much of the protection. The data are highly inferential, and that is frustrating about the field.

T cells and B cells are likely to respond to spike-protein-based vaccines. If the hypothesis that T cells account for the current protection against severe disease and death is correct, the T-cell targets may change less from one variant to another. The self-amplifying RNA vaccine of Gritstone Bio is targeting a broad array of the SARS-CoV-2 proteins in order to elicit a broad cellular response against T-cell epitopes that are not on the spike protein. According to the company's preliminary analysis, the Omicron variant will have a minimal impact on the T-cell epitopes it had selected for inclusion.

We have to decide how important the antibodies are. The level of protection offered by the vaccine against spike protein is more limited than that offered by the cellular response.

Although the emergence of Omicron has added new uncertainties to the COVID crisis, the collective capabilities of the COVID-19 vaccine developers and their numerous manufacturing partners and suppliers have increased dramatically in the past 12 months. There are still many supply chain bottlenecks that may never be eliminated.

At its current level of activity, vaccine manufacturing is vast. According to a mid-December report from market analysts Airfinity, the industry is estimated to have produced over 11 billion doses of COVID-19 vaccine by the year 2021.

New manufacturing innovations will increase capacity, flexibility and speed. Touchlight, which is pursuing a dual COVID-19 strategy as a vaccine developer and as a contract manufacturing organization, is building a huge DNA manufacturing facility. When it goes live later this year, it will be capable of producing up to one kilogram of DNA per month, all from a manufacturing facility with a footprint of just 7,500 square feet.

The size of the genes they can carry limits the power of plismids. The company's novel synthetic "doggybone" can contain and transfer long stretches of the genes that interest them. Touchlight wants to replace plasmid DNA as the main source of DNA for advanced therapy manufacture.

CureVac, as well as developing its portfolio of mRNA vaccines, is continuing a collaboration with the company. The production environment consists of a self-contained, automated GMP production environment that integrates the production of plasmid DNA, mRNA synthesis and lipid nanoparticles with a yield of about 80,000 doses per week. It could be quickly deployed to contain an outbreak or cater to isolated populations.

The circumstances in which these technologies are being developed and tested are never ideal. Many promising vaccine technologies now in development may still be too early stage to have any impact on COVID-19. The case for alternative vaccine technologies that can be deployed locally stronger than ever is incomplete because of Equitable distribution.

This article was first published on January 19 and is reproduced with permission.