New Technologies for Vaccine Development

The all-encompassing devastation that SARS-CoV-2 has brought to the world has sparked an urgency in improving vaccine development as current standards are not always effective and are also time-consuming. Currently, a virus is implanted into mammalian cells or chicken eggs, followed by incubation, virus inactivation, and finally vaccine production.¹ With this technique, it can take months to produce a vaccine. Within these months, the virus may also have mutated, minimizing the effectiveness of the developed vaccine.² Viruses implanted in chicken eggs may also develop chicken-specific surface proteins. When the vaccines derived from these viruses are injected into humans, humans will create antibodies that have a more chicken-specific protein than human-specific one, affecting the efficacy of the vaccine. Needless to say, there are a number of issues with current methodologies.

Incorporating automation

Codex DNA is tackling some of these issues through its automated approach to developing vaccines. Its BioXp system is capable of synthesizing custom DNA overnight, eliminating the need for cells and eggs to incubate the virus, shortening the virus production process from months to days. It also gives others the ability to generate gene constructs in their own labs. Buyers of the system enter the desired DNA sequences into an online ordering portal, and Codex DNA ships them a reagent cartridge. A benefit of the system is its error correction process. Specific enzymes in the reagent cartridge eliminate undesired mutations, providing highly pure DNA.

Used in 2013 to create vaccines against the H7N9 virus, Codex DNA is now focusing on vaccines for SARS-CoV-2. In recent months, Codex DNA has developed several synthetic SARS-CoV-2 genomes. A benefit of synthetic genomes is that researchers can study viruses and develop potential vaccines without having access to highly regulated biosecurity facilities.

In addition to creating DNA for vaccine development, Codex DNA is also working on methods to generate mRNA for vaccines. In fact, the company has made it possible to generate micrograms worth of mutation-free mRNA. The interest in mRNA stems from the idea that, when one is injected with mRNA, the person’s cells will create proteins that elicit an immune response without the person getting sick. mRNA communicates with cells to ultimately prompt the cells to produce antigens of the particular virus. Once the cells produce antigens, the immune system produces antibodies to target the antigens. mRNA vaccines for SARS-CoV-2 target the virus’s surface spike protein. For addressing other viruses, mRNA vaccines may also target surface proteins. For instance, for influenza, this surface protein may be hemagglutinin or neuraminidase.^3,4

While developing mRNA to create vaccines for SARS-CoV-2 is paramount currently, other conditions, such as influenza and tuberculosis (TB), would also benefit from rapid, mutation-free mRNA synthesis. Pfizer, in partnership with German biotech company BioNTech, is working on developing a RNA-based flu vaccine that does a better job at producing antibodies that can tackle flu strains.² Moderna is also working on an mRNA-based influenza vaccine. Moderna’s plan is to combine an influenza vaccine with vaccines for SARS-CoV-2, respiratory syncytial virus, and human metapneumovirus.⁴ The rationale for such a combination is for one shot to produce antigens of all the conditions to elicit a broad immune response.

Unfortunately, little research has gone into improving TB vaccines, with TB killing 1.5 million people annually.³ In fact, only one licensed vaccine exists against TB, the Bacillus Calmette–Guérin (BCG). However, since TB, like SARS-CoV-2, is a respiratory infection, progress in developing mRNA-based SARS-CoV-2 vaccines may lead to mRNA-based TB vaccines.

Novel reagents

The Native Antigen Company (TNAC), part of LGC Clinical Diagnostics, is another company that is doing its part to address the shortcomings of current vaccine development. According to James Shore, Technical Product Manager at TNAC, “Through 2020, The Native Antigen Company was almost entirely focused on developing SARS-CoV-2 reagents to support the research and development of diagnostics and vaccines.” Shore, however, admits that it’s a “balancing act” meeting the needs of the pandemic without sacrificing the needs of research and development for other infectious diseases. To this end, the company has made sure to stay up to date on developing new reagents for seasonal influenza vaccines, “working with flu vaccine manufacturers to develop bespoke reagents that match specific strains or subtypes.”

TNAC sees the benefit of developing mRNA-based vaccines, with Shore noting that many of their reagents are used “for a range of applications, including as immunogens in preclinical testing, and in the development of serological assays for testing patient responses in clinical trials.”

While existing vaccines are effective in neutralizing variant SARS-CoV-2 spike proteins, Shore admits that a vaccine that is effective against unknown future variants may not be well served by vaccines for known variants. He notes that there are groups developing universal vaccines that protect against all SARS-CoV-2 variants, though. It is likely that such vaccines are also being developed for other conditions that have variants.

References

1. Pfizer.com “New RNA Technology Could Get the Flu Vaccine Right, Every Year” Pfizer 2022.

2. Cumbers, John. “This Company Is Fast-Tracking Vaccine Development With the First Fully Automated Gene Synthesis Platform” Forbes.com 22/05/20.

3. Mole, Beth. “mRNA vaccine technology moves to flu: Moderna says trial has begun” ARS Technica 7/7/21.

4. “Codex DNA expands DNA and mRNA synthesis automation” MLO Online. 5/6/21.