COVID-19 vaccines as a way out of the crisis

Prof. Dr. med. Daniel Paris, Director, Department of Medicine at the Swiss Tropical and Public Health Institute, University of Basel, held a talk about the COVID-19 pandemic, including his views regarding the potential implications of the new virus variants first identified in the United Kingdom, South Africa and Brazil and what measures should be taken, during a webinar hosted by BB Biotech in early February. Below is a summary of his remarks:

What we have observed so far is that the mutations are mostly concentrated in spike proteins on the surface of the SARS-CoV-2 virus, which is significant because these spike proteins are also the main target of the currently approved vaccines. Such mutations can make it easier for the SARS-CoV-2 virus to evade the body’s immune response because antibodies (especially neutralizing antibodies) can longer bind as easily to the virus and then eliminate it. Such escape mutations could weaken the immune response and allow the coronavirus to spread more easily. Higher viral loads are often associated with increased transmissibility. The first Phase III vaccine studies based on data/samples taken from regions with a higher incidence of viral variants have already revealed a decrease in the vaccines’ rate of effectiveness. Consequently, the concept of herd immunity via vaccine-induced immune responses will have to be reconsidered. To neutralize a higher infectivity and achieve natural herd immunity, a higher immunity threshold might be necessary. Up to now this threshold has been calculated to range between 60% and 65% of the population. Future vaccination strategies against COVID-19 could display a cyclical or seasonal pattern, as already is the case regarding the seasonal flu. This would mean redesigning a vaccine to match the currently circulating strains of the virus.

«Future vaccination strategies against COVID-19 could display a cyclical or seasonal pattern, as already is the case regarding the seasonal flu»

Diagnostic testing plays a critical role in the rapid identification of emerging hot spots of coronavirus infection. In the context of COVID-19, three main types of tests are being used: molecular PCR tests, antigen tests and antibody tests. The currently employed PCR and antigen test samples, however, must be processed in a lab. Antibody tests require a blood sample. The market potential for easy-to-use diagnostic test kits for self-testing at home, or in senior care facilities, schools or at large events, or when traveling, for example, is far from tapped. The DAVINCI consortium in Switzerland was formed by academic institutions and private-sector partners to develop a complete at-home test for COVID-19. Saliva samples are tested for antigens and antibodies and the results are processed by a simple smartphone app. After a successful proof-of-concept study in 2020, development of the test kit is expected to be completed by the end of 2021. The test kit could also be used as a testing platform for other infectious diseases such as influenza.

«Another advantage of the mRNA vaccines is that they can be quickly redesigned to match new seasonal variants and they have minor side effects»

The development of prophylactic vaccines for COVID-19 over the past twelve months was quite impressive. In early February there were 63 clinical vaccine trials underway, including 22 pivotal Phase III studies. Ten vaccines have already been granted marketing authorization. Three basic technologies are being used to develop these vaccines. Viral vector vaccines, using modified viral vectors as a delivery system, can trigger a strong immune response. The single-shot vaccines developed by AstraZeneca and Janssen have efficacy percentages of 70% and 66%, respectively, but they are much less effective against the emerging virus variants. The two mRNA vaccines developed by Moderna and Biontech/Pfizer that were the very first vaccines to be approved by regulators demonstrated very high efficacy of 94% and 95%, respectively. Another advantage of the mRNA vaccines is that they can be quickly redesigned to match new seasonal variants and they have minor side effects. A disadvantage is that they must be stored at very cold temperatures of minus 20˚ to minus 70˚ C. The authorized protein-based vaccines consisting of proteins and adjuvants have proven to be effective against influenza and human papilloma viruses and also demonstrated a high efficacy against COVID-19, but they are likewise not as effective against the recently identified coronavirus variants.

Data available so far does not yet allow for a conclusive analysis of the durability of the immune responses induced by vaccines. A comparison of data from placebo and treatment groups after the first injection of an mRNA vaccine has indicated that with this type of vaccine there might be a latency period of up to twelve weeks for the second dose. Effective, durable immunity to COVID-19 will largely depend on how quickly vaccines can be redesigned to match mutated protein spikes on the surface of the coronavirus. Inhalers and nasal sprays are likely to figure prominently as a means of making the administration of the vaccine more patient-friendly.