Following the success stories of the Pfizer and Moderna mRNA vaccines for COVID-19, many thought mRNA vaccines paved the way for the future of immunisation. These theories may be faced with a setback as phase-III trials of fellow mRNA vaccine candidate CureVac has achieved subpar results.
CureVac, based in Tübingen, Germany, announced data from the trial on June 16th from a study group of 40,000. The results showed that its two-dose vaccine was just 47 percent effective at preventing COVID-19. Hopes were abundant that CureVac’s attempt at an mRNA vaccine would prove far cheaper than that of Pfizer and Moderna’s vaccines, though measures to improve cost efficiency may have led to the apparent downfall of the vaccine candidate.
mRNA vaccines differ from conventional vaccines in that they are entirely synthetic. Whereas a typical vaccine will use a weakened or dead strain of a disease to allow recognition within the body’s immune system, mRNA vaccines do not use any pathogenic material. Instead, mRNA vaccines operate by teaching cells within our body to produce a protein, or even part of a protein, which will trigger an immune response should the body ever be exposed to the real pathogen.
Thus far, two mRNA vaccines have been approved that have both shown promising results — one from Pfizer, another from Moderna. The Pfizer vaccine has displayed ninety percent efficacy following the interim analysis of Pfizer’s phase-III COVID-19 vaccine trial. 95 percent efficacy was reported after the final analysis of Pfizer’s Phase-III COVID-19 vaccine trial. The efficacy in adults above the age of 65 was determined to be over 94 percent while 9/10 severe cases of COVID-19 were observed in the placebo group.
Two key aspects of the mRNA vaccine production differed in the CureVac vaccine compared to competitors. Firstly, the vaccine was expected to last longer in refrigerated storage than competitors. Pfizer’s vaccine candidate, for example, requires subzero storage temps (-70°C), making it difficult to deliver to rural areas that lack cold-chain capacity. The CureVac vaccine, however, was expected to be able to remain viable in regular refrigerated conditions, which would have allowed greater rollout in the context of developing nations.
It was found, however, that CureVac’s vaccine provoked common inflammatory reactions that were not observed within the other vaccine candidates. It has been speculated by Nature that “the higher storage temperature of CureVac’s jab might have accelerated the breakdown of mRNA in the vial, yielding pieces of genetic code that would raise immune hackles.”
The second key difference is in the encoded spike protein — the component from COVID-19 that is embedded into the mRNA strand in order to provoke an immune response. Both the Moderna and Pfizer vaccines use modified RNA, incorporating an mRNA nucleotide called pseudouridine, CureVac have taken an alternative approach, choosing not to modify the protein, instead leaving the original uridine nucleotide.
According to Nature, “proponents of modified mRNA have long argued that the chemical adjustment is integral to the success of the vaccine technology. Drew Weissman, an immunologist at the University of Pennsylvania who co-discovered the importance of pseudouridine in this context in the mid-2000s, describes it as the “best platform for antibody and neutralisation levels”.”
Despite the setbacks, it is unlikely that mRNA vaccination technology will be shelved given the successes of other companies in the area. The COVID-19 pandemic has brought mRNA vaccines to the forefront of the world’s immunological response to disease. Harvard Health Blog succinctly underlines the sheer speed of the vaccine development efforts
“Within weeks of identifying the responsible virus, scientists in China had determined the structure of all of its genes, including the genes that make the spike protein, and published this information on the Internet…Within minutes, scientists 10,000 miles away began working on the design of an mRNA vaccine. Within weeks, they had made enough vaccines to test it in animals, and then in people. Just 11 months after the discovery of the SARS-CoV-2 virus, regulators in the United Kingdom and the US confirmed that an mRNA vaccine for COVID-19 is effective and safely tolerated, paving the path to widespread immunisation. Previously, no new vaccine had been developed in less than four years.”
Modern genome mapping technology can allow rapid development of an mRNA vaccine in response to sudden outbreaks or mutations within a pathogen. Providing the genome has been mapped and the antigens of the pathogen are understood, an mRNA script can be generated. According to Pfizer, this process could take as little as a week to complete.
Sanofi chief executive officer Paul Hudson suggests, in an interview with Barron’s, that mRNA vaccines will come to dominate the landscape of pandemic reaction due to their capacity for rapid response time. He does, however, believe that mRNA vaccines will struggle in more established markets such as that of flu vaccination. “I think in a pandemic where speed is one of the key ingredients, I think we have to accept that in a single antigen pandemic, mRNA is probably the first go-to.”
India is reportedly “on the cusp” of approving the Pfizer vaccine, indicating an interest in adding mRNA vaccinations to their list of approved vaccines. Given the ease of production of these vaccines, with the technology forming a backbone along which new vaccines can be created simply by adding in the necessary genomic sequence, it may be the case that India soon adds its own vaccine production powerhouses to the fray. Such a combination of ease of creation of new vaccines, along with the bulk production capacity in India could prove invaluable should another pandemic arise.