Vaccine Technologies for Covid-19

Vaccine Technologies for Covid-19

A Scientist turned Consultant explains

Navigating all the different approaches that are being used for developing vaccines against SARS-CoV-2 might be intimidating for non-scientists (and also for some scientists). Here we provide you a summary of all the technologies in use, their mechanism, and some PROs and CONs.

Glossary

  • SARS-Cov-2: virus of the coronavirus family, causative agent of Covid-19
  • Immune system: a complex network of cells, tissues, organs, and the substances they make that helps the body fight infections and other diseases
  • Vaccine: a substance used to stimulate the production of antibodies and provide immunity against one or several diseases, prepared from the causative agent of a disease, its products, or a synthetic substitute, treated to act as an antigen without inducing the disease
  • Antibody: a blood protein produced in response to and counteracting a specific antigen

Introduction

The Covid-19 pandemic has been so disruptive for both the global health and the global economy that it abruptly and dramatically highlighted society’s need for fast and reliable vaccine technologies. The world governments, international health organizations and agencies, the pharmaceutical industry, and the scientific community as a whole responded to this need and the result of these efforts brought to the market a plethora of different vaccine formulations in a record-shattering short development and approval times.

SARS-CoV-2 Mode of Action

SARS-CoV-2 is a virus that belongs to the coronavirus family and upon infection causes the covid-19 disease. The main feature of this virus is a protein that covers its whole surface, called “spike” protein. SARS-CoV-2 uses these spike proteins to enter the human cells, by interacting with protein receptors on these cells in a “lock and key” type interaction. Upon entrance in the human cells, the virus can continue its life cycle of replication and infection of other cells and as a consequence cause the covid-19 disease.

Vaccine Technologies for SARS-Cov-2

All vaccines technologies against the SARS-CoV-2 virus share the same goal: to teach the immune system how to mount an antibody response against this virus, especially focusing on a prominent feature, its surface spike proteins. In vaccinated individuals, upon contact with the SARS-CoV-2 virus, is triggered an antibody response able to recognize and neutralize the virus, effectively preventing an infection or in the worst case, avoiding the most life-threatening symptoms of the infection.

The main vaccine technologies currently on the market or awaiting approval belong to four different categories: whole virus based, viral vector based, nucleic acids based, and protein based.

Whole-Virus based Vaccines - The classic strategy

These vaccines use whole viruses to teach the immune system to produce antibodies against it. The viruses are first grown in culture and then either completely killed (“inactivated” whole virus vaccines) or weakened (“attenuated” whole virus vaccines) so that they are not harmful anymore. Once into the body of the people receiving the vaccine, these either dead or weak viruses’ spike proteins are recognized by the immune system, which then mounts an antibody response.

This technology has been used since the onset of vaccine development, pioneered by Edward Jenner in the late 18th century, therefore is well established, robust, effective, and with well-known safety profiles. These formulations are usually stable at refrigerator temperatures, therefore do not require ultra-cold (around -70 °C) chain.

One drawback is that for killed virus formulations, big amounts of starting material (e.g. the virus) are needed, and this could greatly impact the manufacturing costs. A second drawback is that immunocompromised individuals might not be able to tolerate even weakened viruses.

PROs:

  • Highly effective
  • Well-established technology
  • Safe and well tolerated
  • Relatively temperature stable

CONs:

  • Killed viruses, a lot of material is needed
  • Weakened virus not suitable for immunocompromised individuals
  • Booster shots may be required

Whole virus based vaccines that have been approved to date in various countries:

  • Covaxin (Bharat Biotech, India)
  • CoronaVac (SinoVac, China)
  • BBIBP-CorV (Sinopharm, China)

Viral-Vector based Vaccines - The big Breakthrough

These vaccines aim at introducing into the body the genetic blueprint for producing SARS-CoV-2 spike proteins, without the rest of the genetic information of the virus. They do it by having another virus as a carrier (a “vector”) and this other virus is a harmless and common virus like the one that causes common cold. This way the harmless vector virus, carrying the genetic blueprint for producing SARS-CoV-2 spike proteins, upon injection causes the production of the spike proteins, which are recognized by the immune-system and trigger the development of antibodies.

Albeit very few viral vector-based vaccines are on the market, this technology is extremely well-established and has been studied for years in clinical trials. As a result, these vaccines have a very robust efficacy and safety profile and had a big breakthrough during the SARS-CoV-2 vaccine development race, aided by the fact that they do not require ultra-cold chain.

PROs:

  • Highly effective and specific
  • Well-established technology
  • Potential of long-term protection
  • Relatively temperature stable

CONs:

  • Potentially less effective if population has existing protection to viral vector
  • Potentially not cost-effective (based on virus production capabilities)

Viral vector based vaccines that have been approved to date in various countries:

  • Sputnik V (Gamaleуa, Russia)
  • JNJ-78436735 (J&J, USA - currently paused)
  • Covidshield (Oxford/Astrazeneca, UK/Sweden)
  • Ad5-nCoV (CanSino Biologics, China)

Nucleic-Acid based Vaccines - The new kid on the block

Much like in the case of the viral vector-based vaccines, the aim of nucleic acids-based vaccine is to introduce into the body only the genetic blueprint for producing SARS-CoV-2 spike proteins and nothing else. In particular, mRNA vaccines use the nucleic acid molecule mRNA carrying the blueprint for the spike protein. Since RNA is a highly unstable molecule that degrades easily, these nucleic acids are packed into a layer of fatty droplets, which both protects them and helps them make into the body where the blueprint can be read, spike proteins produced and recognized by the immune system, and an antibody response is triggered.

Once labelled “Next generation vaccines”, nucleic acids-based vaccines are finally put to the test and so far, they seem to deliver. The data on their effectiveness and safety coming from the clinical trials and the first waves of immunization of the public are extremely promising. This, combined with the big advantage in terms of speed of design and development of this type of vaccines, gives them the potential to become the go-to vaccine technology to reach for in a pandemic scenario. The major drawback of nucleic acids-based vaccines, especially RNA ones, is that they often require ultra-cold chain which may impact the logistics.

PROs:

  • Highly effective
  • Safe
  • Fast development

CONs:

  • Boosters may be required
  • Expensive starting materials
  • Some require ultra-cold chain

Nucleic acids-based vaccines that have been approved to date in various countries:

  • BNT162b2 (BioNTech/Pfizer, USA/Germany)
  • mRNA-1273 (Moderna, USA)

Protein-based Vaccines - Late to the game

As the name suggests, protein-based vaccines introduce into the body proteins, in this case mainly SARS-CoV-2 spike proteins, which are recognized by the immune system and trigger antibody development. These proteins can be either lab-produced spike protein biosimilars or a cocktail of proteins that arrange themselves in a virus-like shape.

Protein-based vaccines present several advantages, they are a well-established technology, with a strong effectiveness and safety profile and they do not require ultra-cold chain. Their biggest drawback, which caused this technology to miss the chance of being part of the first wave of SARS-CoV-2 vaccines, is their long design and development times. Moreover, some of the protein-based vaccines require a relatively complex manufacturing process.

PROs:

  • Highly effective
  • Safe
  • Well-established technology
  • Relatively stable

CON's:

  • Long development time
  • Relatively complex manufacturing

Protein based vaccines with pending approval to date in various countries:

  • NVX-CoV2373 (Novavax, USA)

Outlook

The vaccine development field has made tremendous progress during the Covid-19 pandemic, and all these different vaccines that are now available, are the tangible proof. Expanding the number of vaccine technologies at our disposal will not only make us more resilient in case of another pandemic, but also provide us with vaccines against other diseases that have not yet been tackled.