|Year : 2021 | Volume
| Issue : 1 | Page : 17-23
Efficacy and effectiveness of COVID-19 vaccines: Progress and prospect
Yifan Li, Jiahai Lu
School of Public Health; One Health Center of Excellence for Research and Training; Key Laboratory for Tropical Disease Control of Ministry of Education; NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Sun Yat-Sen University, Guangzhou 510080, China
|Date of Submission||26-Sep-2021|
|Date of Decision||30-Sep-2021|
|Date of Acceptance||13-Oct-2021|
|Date of Web Publication||03-Nov-2021|
School of Public Health; One Health Center of Excellence for Research and Training; Key Laboratory for Tropical Disease Control of Ministry of Education; NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Sun Yat-Sen University, Guangzhou 510080
Source of Support: None, Conflict of Interest: None
To prevent and control COVID-19, COVID-19 vaccines are being developed, tested, and approved at an unprecedented rate. As of September 24, 2021, 22 types of COVID-19 vaccines have been approved for conditional marketing or emergency use by at least one country worldwide. Vaccine efficacy/effectiveness is a crucial concern for vaccination. This article provides an overview of efficacy of phase III clinical trials, vaccination, effectiveness of real-world studies as well as challenges of COVID-19 vaccine.
Keywords: COVID-19; Vaccine; Vaccination; Efficacy; Effectiveness
|How to cite this article:|
Li Y, Lu J. Efficacy and effectiveness of COVID-19 vaccines: Progress and prospect. One Health Bull 2021;1:17-23
| 1. Introduction|| |
Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to ravage the world. According to the emerging infectious diseases surveillance system of One Health Center of Excellence for Research and Training of Sun Yat-sen University, as of 8:58 am on September 26, 2021, the cumulative number of confirmed cases in the world had exceeded 232.11 million, with the United States, India, and Brazil accounting for 42.49%. The cumulative death toll has exceeded 4.75 million, with the United States, Brazil, and India accounting for 36.75%, posing a serious threat to global public health and social economy. Therefore, it is expected to develop a safe and effective treatment or vaccine to control the spread of SARS-CoV-2.
Vaccine is one of the most successful and cost-effective health interventions for the prevention of infectious diseases worldwide. According to a study published in Lancet, hepatitis B virus, haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, serogroup A Neisseria meningitidis, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever have a significant impact on human health. Vaccinations against these 10 pathogens have saved more than 37 million lives in 98 low- and middle-income countries between 2000 and 2019. In addition to direct protection for vaccinators, vaccination can also provide indirect protection for non-immune individuals when vaccination coverage reaches a certain level, especially for those who cannot be vaccinated due to health conditions such as allergy to vaccines, which is called herd immunity or community immunity.
Smallpox, which has been spread for thousands of years in human history, is an example of how smallpox virus transmission was interrupted and eliminated through herd immunity. In 1967, the World Health Organization launched the Intensified Smallpox Eradication Programme, and mass vaccination against smallpox was carried out globally. On 8 May 1980, the 33rd World Health Assembly officially declared that the goal of global eradication of smallpox had been achieved. A study by Milman et al., published in Nature Medicine, found that 20% of the population vaccinated with BNT162b vaccine in 177 communities in Israel brought a two-fold decrease in the positive rate of SARS-CoV-2 in the unvaccinated population, suggesting that COVID-19 vaccination protects the unvaccinated population. Hence, it is very likely to achieve herd immunity by building an immune barrier through vaccination. Therefore, herd immunity is an important means for the prevention and control of infectious diseases, and it is of great significance for the prevention and control of COVID-19 to realize herd immunity through the universal vaccination of the public with a safe and effective COVID-19 vaccine. This article summarizes the efficacy of phase III clinical trials, vaccination and real-world studies of COVID-19 vaccines, and analyzes the challenges and responses.
| 2. Efficacy of COVID-19 vaccine in phase III clinical trials|| |
SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus, which belongs to the family beta coronavirus (βCoV). The total length of the genome is about 30 kb, of which 20 kb is the non-coding region and 10 kb is the coding region of viral proteins, including structural proteins and non-structural proteins. The former includes spike protein (S), nucleocapsid protein (N), membrane protein (M), and envelope protein (E). SARS-CoV-2 binds to human angiotensin-converting enzyme Π mainly through the S1 subunit C-terminal of S protein, activates endocytosis, and makes it enter human cells, thus initiating signals related to virus replication and proliferation. Therefore, S protein is a crucial target for vaccine design and development.
According to WHO statistics, as of 24 September 2021, 315 types of COVID-19 vaccines were in development globally, of which 194 were under preclinical studies and 121 during human clinical trials. Simultaneously, 7 types of vaccines have been included in Emergency Use Listing, which are BNT162b2, AZD1222, Covishield, Ad26.COV2.S, mRNA-1273, BBBIBP-CorV and CoronaVac.
At the end of 2020, Pfizer Inc and BioNTech SE were the first to disclose data of phase III clinical trials of their joint mRNA vaccine BNT162b2. The vaccine is safe and meets the safety criteria for emergency use authorized by the Food and Drug Administration. Besides, the efficacy rate of vaccines is 95%, and 94% for people over age 65. Another vaccine from America developed by Moderna, named mRNA-1273, has an efficacy rate of over 90% against SARS-CoV-2, reaching 94.1%. The data of phase III clinical trials of the inactivated COVID-19 vaccines developed by Sinovac and Beijing Bio show that the efficacy rate in preventing symptomatic infection of SARS-CoV-2 is 67% and 78.1%, respectively,. The efficacy rate of other COVID-19 vaccines approved for conditional marketing or emergency use ranged from 60% to 90%, and the overall efficacy rate of mRNA vaccines was higher than that of other vaccines, as summarized in [Table 1]. On 27 May 2021, Pfizer-BioNTech announced in NEJM that the BNT162b2 vaccine had a 100% efficacy rate in phase III clinical trials among adolescents aged 12-15 years, indicating that BNT162b2 is highly effective in the 12-15 age group. In September 2021, NEJM consecutively published the clinical trial results of BNT162b2 for 6 months and mRNA-1273 for 5 months, and BNT162b2 showed a 91.3% efficacy rate against SARS-CoV-2 and 96.7% efficacy rate among severe cases at 6 months after vaccination. The efficacy rate of mRNA-1273 in the prevention of symptomatic infection of COVID-19 was 93.2%, and that of severe disease was 98.2%. Two follow-up studies of phase III clinical trials of mRNA vaccines showed that efficacy rate decreased over time, but the vaccine remained effective.
| 3. COVID-19 vaccination status|| |
COVID-19 vaccination is the largest vaccination campaign in human history. In mid-December 2020, the first batch of COVID-19 vaccines began to be administered to key groups in many locations around the world. With the launch of COVID-19 vaccines and the continuous improvement of production capacity, vaccination is being carried out in an orderly manner and the coverage of vaccination is expanding. Countries basically adopt government-led, free vaccination, voluntary, and batch vaccination mode. As of 25 September 2021, more than 6.10 billion doses of novel coronavirus vaccine have been administered in 217 countries and regions, with 79 doses of COVID-19 vaccine per 100 people. China has received more than 2.19 billion doses of COVID-19 vaccine, accounting for about one-third of the global volume. There are significant differences in the progress of COVID-19 vaccination in different countries. The current top 18 countries and regions in the world in terms of vaccine coverage as of September 25, 2021 are shown in [Figure 1].
|Figure 1: The vaccination status of the top 18 countries and regions in the world as of September 25, 2021 in terms of COVID-19 vaccination coverage.|
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| 4. Real-world effectiveness of COVID-19 vaccines|| |
Clinical evidence generated by vaccine clinical trials tends to show the clinical value of vaccines under ideal conditions, and it especially emphasizes the strict and prudent approval process. Real-world data generated by real-world studies are more close to vaccination in the real world and have a more important role in evaluating the effectiveness of vaccines in the real world. The phase III trial is intended to further verify the safety of the vaccine and provide a preliminary answer to its effectiveness, which will also be critical from the real world after many COVID-19 vaccines are officially approved for vaccination. Evaluating the effectiveness of COVID-19 vaccine of the real world includes safety, direct protection to the inoculator, indirect protection to the non-vaccinated, protection effectiveness to the mutant virus strains etc. Vaccination policy and COVID-19 prevention & control policy are formulated with the help of scientific data, which plays a vital role to the overall prevention and control on COVID-19 pandemic.
A number of published real-world studies from the United States and other countries have shown that the two mRNA vaccines developed in the United States, BNT162b2 and mRNA-1273, provide more than 75% efficacy against the original and mutant SARS-CoV-2 strains in different populations. The effectiveness of British adenovirus vector vaccine ADZ1222, Chinese inactivated vaccine CoronaVac and Chinese Bio SARS-CoV-2 vaccine against original and mutant SARS-CoV-2 strains can also exceed the 50% minimum threshold of COVID-19 vaccine effectiveness set by WHO, as summarized in [Table 2]. A report published by the Israeli Ministry of Health on 22 July 2021 showed that the effectiveness of mRNA vaccine BNT162b2 was 39% against COVID-19 when the Delta was the dominant strain, contradicting with vaccine effectiveness studies for the Delta strain in other countries, but vaccine showed 88% protection against hospitalizations and 91% protection against severe disease. Based on a real-world study of COVID-19 in Guangzhou from May to June 2021, the results showed that the protection of two inactivated Chinese vaccines against moderate symptomatic COVID-19 was 70.2% against the Delta strain and up to 100% against severe cases (Due to the small sample size of severe cases, the protective effect of severe cases may be overestimated). Although the COVID-19 vaccine is less effective in preventing SARS-CoV-2 infection in response to the novel coronavirus variant, it still provides better protection against COVID-19-related hospitalizations, severe illness and death. It is important to note that the effectiveness of different vaccines cannot be directly compared in strict terms due to differences in study design, location, population, endpoints and prevalence of novel coronavirus strains at the time of study.
|Table 2: Effectiveness data from real-world studies of COVID-19 vaccines.|
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| 5. Challenges and prospects|| |
SARS-CoV-2 is an RNA virus. Due to the lack of mismatch repair mechanism during DNA virus replication, virus replication is accompanied by high mutation rate. SARS-CoV-2 is highly contagious, and studies have shown that patients with SARS-CoV-2 have lower levels of neutralizing antibodies than patients with SARS-CoV. The disease lasts longer and is better able to evade the human immune response, especially the SARS-CoV-2 variant[45-47]. WHO has been monitoring and assessing novel coronavirus variants worldwide since January 2020, and novel coronavirus variants have been classified as follows: Variants of Concern (VOC), Variants of Interest (VOI) and Alerts for Further Monitoring. Four worrying variants, Alpha, Beta, Gamma and Delta, have spread rapidly around the world, and several real-world studies have shown that vaccines are reducing the protection rate against mutated strains, which brought much uncertainty to COVID-19 prevention and control globally. As of mid-September 2021, 13 countries, including the United States, France, Germany, the United Arab Emirates and Israel, have initiated or announced enhanced immunization programs for priority populations, with more than 30% of the population in Israel having completed the third dose of vaccination. Starting from late September in China, key groups aged 18-59 who have received two doses of inactivated vaccine before March 1, before April 1 and before May 1 are eligible for a third dose of strengthened COVID-19 vaccine in September, October and November, respectively, in accordance with the requirement of six months interval.
In response to the rapid mutation of the novel coronavirus, we should, on one hand, closely monitor the COVID-19 pandemic and the mutation of the virus, cut off the source of infection as soon as possible once cases are detected, and shift the prevention and control from mass prevention and control to targeted prevention and control. On the other hand, there is a need to strengthen the research and development of vaccines that target mutated strains of the virus and have broad spectrum protection. At present, big data research is developing rapidly. Once new virus mutations appear, the common target antigens or receptors can be quickly found via big data mining to guide the improvement of vaccines. Currently, many vaccine manufacturers and research and development teams around the world have deployed vaccines against the mutant strains of the virus. Nathan et al. identified mutationally constrained SARS-CoV-2 epitopes that can be recognized by immune cells known as T cells by using structure-based network analysis. And, these epitopes could then be used in a vaccine to train T cells, providing broad protective immunity against SARS-CoV-2 and its variant strains. T-cell vaccines provide a new possibility for the prevention and control of SARS-CoV-2 variants and similar coronaviruses in the future.
One challenge in evaluating vaccine effectiveness is the lack of detailed data that is publicly available, with many results published only in press releases rather than in peer-reviewed journals, making it difficult for outside experts to fully assess them. We should break down barriers, promote international collaboration on COVID-19 research, speed up the cycle of journal peer review, and share data in a timely manner to jointly address future challenges.
COVID-19 has brought unprecedented challenges to mankind, and the speed of global COVID-19 vaccine development and approval is unprecedented as well. As a public health product for the prevention and control of COVID-19 worldwide, COVID-19 vaccine is safe, effective, controllable and accessible, which is of great significance for improving global vaccination coverage and building a herd immunity barrier as the earliest possible time.
Conflict of interest statement
The authors declare that there is no conflict of interest.
We would like to thank Jinjin Liu for the help in language.
It is supported by the National Key Research and Development Project (No.2018YFE0208000) and the Research and Development Program in Key Fields of Guangdong Province (No.2018B020241002).
Lu JH and Li YF discussed the framework of the article. Li YF was responsible for literature collection and manuscript writing. Lu JH, the corresponding author, reviewed and edited the content of the whole review.
| References|| |
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature
One Health Center of Excellence for Research and Training Sun Yat-sen University. Emerging infectious disease surveillance system at One Health Center of Excellence for Research and Training
. [Online] Available from: http://covid.eidonehealth.com/templates/index.html
. [Accessed on 26 September 2021].
Greenwood B. The contribution of vaccination to global health: Past, present and future. Philos Trans R Soc Lond B Biol Sci
Li X, Mukandavire C, Cucunubá ZM, Londono SE, Abbas K, Clapham HE, et al. Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: A modelling study. Lancet
Smith DR. Herd immunity. Vet Clin North Am Food Anim Pract
Lane JM. Mass vaccination and surveillance/containment in the eradication of smallpox. Curr Top Microbiol Immunol
Milman O, Yelin I, Aharony N, Katz R, Herzel E, Ben-Tov A, et al. Community-level evidence for SARS-CoV-2 vaccine protection of unvaccinated individuals. Nat Med
Amanat F, Krammer F. SARS-CoV-2 vaccines: Status report. Immunity
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med
Frenck Jr RW, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med
Thomas SJ, Moreira Jr ED, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. N Engl J Med
2021. doi: 10.1056/NEJMoa2110345.
EI Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, et al. Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase. N Engl J Med
2021. doi: 10.1056/NEJMoa2113017.
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet
Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med
Al Kaabi N, Zhang YT, Xia SL, Yang YK, AI Qahtani MM, Abdulrazzaq N, et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: A randomized clinical trial. JAMA
Anhui Zhifei Longcom Biopharmaceutical Co., Ltd.. Zhifei Bio. Suggestive announcement on receipt of key data from the Phase Μ clinical trial of the recombinant novel coronavirus vaccine (CHO cells)
. [Online] Available from: http://www.zhifeishengwu.com/news/gsyw/qyyw/2021-08-30/563.html
. [Accessed on 26 September 2021].
Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med
Li XN, Huang Y, Wang W, Jing QL, Zhang CH, Qin PZ, et al. Efficacy of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: A test-negative case-control real-world study. Emerg Microbes Infect
Pawlowski C, Lenehan P, Puranik A, Agarwal V, Venkatakrishnan AJ, Niesen MJM, et al. FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Medince
Pilishvili T, Gierke R, Fleming-Dutra KE, Farrar JL, Mohr NM, Talan DA, et al. Effectiveness of mRNA Covid-19 vaccine among U.S. health care personnel. N Engl J Med
2021. doi: 10.1056/NEJMoa2106599.
Pritchard E, Matthews PC, Stoesser N, Eyre DW, Gethings O, Vihta KD, et al. Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom. Nat Med 2021; 27
Bernal JL, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ 2021; 373:
Hall VJ, Foulkes S, Saei A, Andrews N, Oguti B, Charlett A, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): A prospective, multicentre, cohort study. Lancet
Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med
Haas EJ, Angulo FJ, McLaughlin JM, Anis E, Singer SR, Khan F, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: An observational study using national surveillance data. Lancet
Fabiani M, Ramigni M, Gobbetto V, Mateo-Urdiales A, Pezzotti P, Piovesan C. Effectiveness of the comirnaty (BNT162b2, BioNTech/ Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers, Treviso province, Veneto region, Italy, 27 December 2020 to 24 March 2021. Euro Survei
Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med
Bernal LJ, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med
Sheikh A, McMenamin J, Taylor B, Robertson C, Public Health Scotland and the EAVE Π Collaborators. SARS-CoV-2 Delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. Lancet
Thompson MG, Burgess JL, Naleway AL, Tyner H, Yoon SK, Meece J, et al. Prevention and attenuation of Covid-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med
Jara A, Undurraga EA, González C, Paredes F, Fontecilla T, Jara G, et al. Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. N Engl J
Med 2021; 385
Swift MD, Breeher LE, Tande AJ, Tommaso CP, Hainy CM, Chu HT, et al. Effectiveness of messenger RNA coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a cohort of healthcare personnel. Clin Infect Dis
Pilishvili T, Fleming-Dutra KE, Farrar JL, Gierke R, Mohr NM, Talan DA, et al. Interim estimates of vaccine effectiveness of Pfizer-BioNTech and Moderna COVID-19 vaccines among health care personnel - 33 U.S. Sites, January-March 2021. Morb Mortal Wkly Rep
Domingo E, Holland JJ. RNA virus mutations and fitness for survival. Annu Rev Microbiol
Yuan M, Huang DL, Lee CCD, Wu NC, Jackson AM, Zhu XY, et al. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants. Science
Wu F, Wang A, Liu M, Wang QM, Chen J, Xia S, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv
2020. doi: https://doi.org/10.1101/2020.03.30.20047365
Zhou F, Yu T, Du RH, Fan GH, Liu Y, Liu ZB, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet
Krause PR, Fleming TR, Longini IM, Peto R, Briand S, Heymann DL, et al. SARS-CoV-2 variants and vaccines. N Engl J Med
21st Century Business Herald. Global COVID-19 vaccination is entering its second half: 13 countries have launched booster vaccination programmes, with China starting this month
. [Online] Available from: https://www.163. com/dy/article/GK4FD38N05199NPP.html
. [Accessed on 26 September 2021].
Nathan A, Rossin EJ, Kaseke C, Park RJ, Khatri A, Koundakjian D, et al. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses. Cell 2021; 184
[Table 1], [Table 2]