Vaccines save millions of lives each year from various illnessness1. As we near one year completion mark of the COVID-19 pandemic there have been over 63 million global infections and over 1.4 million deaths2. The consensus among experts is that only an effective vaccine will end this pandemic. Vaccine developers are making rapid progress toward developing a safe and effective vaccine against SARS-CoV-2, the novel coronavirus which causes COVID-19. Data from phase 1 and phase 2 trials are already available for several vaccine candidates, and many have moved into phase 3 trials3 with preliminary results announced in just the last few weeks4-6. Pfizer4, Moderna5, and AstraZeneca6 reported minimal side effects for their vaccines with efficacy rates up to 95% and it is now a matter of weeks-months when these vaccines will become available.
Types of vaccine in development
In general, the vaccine technologies can be divided into ‘traditional’ (live-attenuated or inactivated virus vaccines), recombinant protein and viral vector, and next-generation RNA and DNA approaches7,8.
Live-attenuated vaccines are produced by generating a attenuated version of the virus that does not cause the disease but induces the same immune responses as natural infection. Although live vaccines tend to create strong long-lasting immune response, these vaccines are not recommended for immunocompromised individuals since it is possible for attenuated viruses to cause disease progression in these individuals. As of date, only three live-attenuated vaccines are currently in preclinical evaluation3.
Inactivated virus vaccines
Inactivated vaccines are produced by growing SARS-CoV-2 in cell culture followed by complete inactivation. They can induce a strong antibody response but require large quantities of virus and biosafety containment level 3 large-scale virus production facilities. Several versions of inactivated SARS-CoV-2 have entered clinical trials, with four candidates in phase 3 trials3.
Recombinant protein vaccines
For coronavirus, recombinant protein vaccines are commonly based on the spike protein, a protein present on the surface of the virus that mediates entry into the host cell by binding to the ACE-2 receptor, which is present on human endothelial cells. Other recombinant protein vaccines include receptor-binding domain (RBD) and virus-like particle (VLP) based vaccines. The advantage of recombinant protein vaccines is that they can be produced without handling a live virus and may have fewer side effects than an intact virus. However, such vaccines can also have disadvantages. The spike protein is hard to express, and this is likely to have an impact on production yields. Also, these vaccines may be poorly immunogenic requiring adjuvants to stimulate a stronger immune response. There is only one protein-based vaccine candidate in phase 3 trials, but several others are in phase 1 and/or 2 trials3.
Viral vector vaccines
Viral vector vaccines offer a high level of protein expression, long-term stability and are capable of inducing strong immune responses. These vaccines are typically based on a virus that does not cause human disease and that is engineered to express the SARS-CoV-2 spike protein. A disadvantage is that some of these viral vectors can be neutralized by pre-existing immunity against the viral vector. Several viral vector vaccine candidates have entered clinical trials, with four candidates in phase 3 trials3. Of those, promising early results from an interim analysis of vaccine candidates from AstraZeneca/University of Oxford was just announced6. There are two viral vector vaccines currently licensed, one from CanSino that is currently in use in the Chinese military, and another from Gamaleya Research Institute in Russia, which was licensed without a phase 3 trial7.
Nucleic acid vaccines
Nucleic acid (DNA and RNA) technologies are more recent and offer great flexibility in terms of antigen manipulation and potential for rapid development. However, nucleic acid vaccines may show low immunogenicity, and it is unclear what issues will be encountered in terms of long-term storage stability since they storage at extreme cold temperatures (£ 70° C). Several nucleic acid vaccine candidates (five DNA-based and six RNA-based candidates) have entered clinical trials. Primary efficacy analyses from phase 3 trials have shown that RNA-based vaccine candidates from Pfizer/BioNTech and Moderna/NIAID are safe and 95% effective and both companies have already applied for US and European emergency regulatory approval4,5. The UK regulator has just approved the Pfizer/BioNTech vaccine and the UK has become the first country in the world to approve the first COVID-19 vaccine.
More than 200 vaccine candidates, based on several different platforms, are currently in development against SARS-CoV-2 with 48 candidate vaccines already in phase 3 trials3. There are many different COVID-19 vaccines in development because it is not yet known which ones will be effective and safe and different vaccine types may be needed for different population groups. The World Health Organization (WHO) maintains a working document3 that includes most of the vaccines in development and is available at https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.
About the author:
Lúcia Moreira Teixeira is an expert in Immunology driven by a personal passion for science and the ambition to translate ground-breaking science into innovative life-changing immunotherapies. She is interested in immuno-oncology, autoimmune and infectious diseases. She strongly believes researchers should engage more in science communication. Find her on twitter – @LMTimmunol – or LinkedIn – www.linkedin.com/in/moreirateixeiralucia.
1. WHO. Vaccines and immunization. https://www.who.int/health-topics/vaccines-and-immunization
2. WHO Coronavirus Disease (COVID-19) Dashboard. (Accessed December 3, 2020). https://covid19.who.int/
3. WHO. Draft Landscape of COVID-19 Candidate Vaccines. (Publication of November 12, 2020). https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
4. Pfizer November 18, 2020. Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints. https://www.businesswire.com/news/home/20201118005595/en/
5. Moderna November 30, 2020. Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization.
6. AstraZeneca November 23, 2020. AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html
7. Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020). https://doi.org/10.1038/s41586-020-2798-3
8. WHO. What we know about COVID-19 vaccine development (Publication 6 October 2020). https://www.who.int/publications/m/item/what-we-know-aboutcovid-19-vaccine-development