With a dizzying number of vaccines against Covid-19 in various stages of development, it is hard to keep news and updates straight. Added to the complexity is the fact the vaccines currently under development are quite distinct from one another, and each carries their own questions of safety and efficacy. With demand continuing to surge, the normally slow and arduous process of vaccine research and development has been spurred into an all-out sprint, raising the question of whether vaccines developed at this pace are safe and effective. There are dozens of vaccines in early development, but a few have surpassed early clinical trials and seem to be promising candidates for a vaccine. Here is where we are at with those.
The vaccine currently winning the race is Moderna’s experimental mRNA vaccine mRNA-1273, which this past week finalized its phase III clinical trial protocols, and is set to study a cohort of roughly 30,000 people in July. This phase of trials involves much larger subject groups than phase II trials and seeks to determine long-term efficacy and safety of the vaccine.
The mRNA-1273 vaccine is a new technology that involves introducing genetic material in the form of messenger RNA (mRNA) into the body to serve as a template for production of coronavirus antigens in the body. These antigens are expected to then trigger our adaptive immune response and ultimately protective antibodies. This technology is still relatively new and unproven, but animal studies have shown promising results. The technology relies on shuttling mRNA into cells in the body by enclosing it in a fat-lined nanoparticle that will fuse with our cell’s outer membrane.
Moderna feels confident that they have the capacity to generate as many as a billion doses of the vaccine by 2021
mRNA technology, although not reliably proven, does hold promise for rapid production of vaccines should they pass the later phases of clinical trials. Compared to traditional vaccine development, RNA vaccines can be developed quite rapidly. Moderna feels confident that they have the capacity to generate as many as a billion doses of the vaccine by 2021.
University of Oxford: ChAdOx1
The University of Oxford in conjunction with British pharmaceutical company AstraZeneca is moving into phase II/III trails for their recombinant adenovirus vaccine against SARS-CoV-2. This vaccine, called ChAdOx1 (also named ADZ1222) packages the genetic material synthesized from coronavirus antigens into a modified adenovirus. Once introduced into the body, the modified adenovirus will be able to penetrate human cells and introduce the coronavirus RNA without causing any disease. Once introduced, the viral genetic material will be translated into antigen proteins, thus eliciting an immune response.
The ChAdOx1 vaccine has shows some preliminary efficacy in generating antibodies in monkeys.
Recombinant virus vaccines are a relatively labor intensive vaccine development method, though designing them in this way ensures a more efficient transfer of viral genetics when compared to RNA/DNA virus technologies. AstraZeneca secured an agreement with the Inclusive Vaccines Alliance to provide large scale production of the virus. Pascal Soriot, Chief Executive Officer at AZ said in a press release, “This agreement will ensure that hundreds of millions of Europeans have access to Oxford University’s vaccine following approval.”
One of the earliest biotech companies to enter the vaccine race was CanSino with another modified adenovirus vaccine against Covid-19. The vaccine AD5, which uses similar technology as the Oxford vaccine has moved out of phase I trials and is set to begin phase II trials in China this summer.
Adenovirus vaccines can be a double edge sword. Since by using the adenovirus (modified) that expresses both its own antigens as well as antigens from SARS-CoV-2 engineered into it, it poses the possibility that it may induce some level of immunity to both adenoviruses — which cause a range of human diseases from cold-like syndromes to pink eye — as well as coronavirus, making these vaccines a potentially valuable advancement. On the flip side, because adenoviruses are relatively common, some people may have already been exposed to them, which would lessen the response to the modified adenovirus vaccine. In fact, CanSino found that roughly half of their participants showed a muted response to the vaccine.
The Chinese biotech company Sinovac is putting its efforts into the time-tested vaccine technology that utilizes inactivated virus as its mode of vaccination. SARS-CoV-2 viruses were isolated from infected people and cultured and later inactivated to be tested as vaccines. This technology has a long history dating back to early experiments with immunity leading up to Jonas Salk’s development of a polio vaccine in the 1950’s, which contained inactivated polio virus.
Sinovac released the results of their phase I/II trials in a press release that showed that the PiCoVacc vaccine induces antibody production against SARS-Cov-2 within two weeks.
Sinovac is also preparing to move the PiCoVacc vaccine into phase III trails some time this summer.
Whole inactivated viral vaccines come with some drawbacks as well. Because they require the isolation, culture and modification of whole viruses, they are time and labor intensive and difficult to develop quickly on a mass scale. Because a Covid-19 vaccine is needed as soon as possible, this vaccine technology has been criticized as too slow to meet this demand.
Keeping up with Covid-19 vaccine development is a challenging process. Never before in history have we seen such rapid and widespread effort to develop a vaccine. History has shown that vaccines are traditionally difficult and time consuming to develop, but researchers and governing bodies are hoping that these groups are able to break with history and produce a much-needed vaccine against Covid-19 by 2021.