COVID-19 aşıları: güncel veriler ve gelecek perspektifi

Öz

Şiddetli akut solunum sendromu koronavirüs 2’nin (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) neden olduğu koronavirüs hastalığı (coronavirus disease-19; COVID-19), insanlarda şiddetli klinik bulgulara ve ölümlere yol açmış, ülkelerin sağlık sistemlerini etkilemiş ve tüm dünyada beklenmedik pek çok sorunlara neden olmuştur. Henüz tedavisi geliştirilmemiş olan viral hastalıklarla mücadelenin en etkili yolu olan aşılama, COVID-19 ile mücadelede de öncelikli adım olarak görülmüş ve pandeminin başında pek çok ülke ve firma aşı geliştirme çalışmalarına hızla başlamıştır. Günümüzde COVID-19’a karşı pek çok farklı tipte aşı geliştirilmiş ve onaylanıp ticari hale dönüşmüştür. Ticari aşıların yanı sıra farklı tipte ve farklı teknolojilere sahip aşı geliştirme çalışmaları halen devam etmekte ve bu aşıların enjeksiyon harici intranazal gibi farklı uygulama yollarının test edilmesine ilişkin çalışmalar bilim insanları tarafından sürdürülmektedir. Pandemi ile birlikte, ulusal aşı üretiminin önemi net bir şekilde anlaşılmıştır. Bu bağlamda ülkemizin, aşı geliştirme çalışmalarına ve yatırımlarına destek ve öncelik vermesi, aşı üretim tesislerinin sayısının ve kapasitelerinin arttırılması, bu kurumlarda çalışacak kalifiye personel ve konusunda uzman bilim insanlarının yetiştirilmesi hususlarına yönelik stratejik bir planlama ile hareket etmesi gerekmektedir.

Anahtar Kelimeler

• Aşı
• COVID-19
• SARS-CoV-2

COVID-19 vaccines: current data and future perspective

Öz

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to severe clinical symptoms and deaths in humans, affected the healthcare systems and resulted in many unexpected issues globally. Vaccination, which is the most effective way to combat viral diseases that effective treatment has not yet been developed, was a priority step in the fight against COVID-19, and many countries and companies promptly started to studies for vaccine development at the beginning of the pandemic. Currently there are many types of vaccines developed and commercially available after approval. In addition to commercially available vaccines, vaccine development studies still carry on with different types and technologies, and studies on testing different administration routes of these vaccines such as intranasal route are carried out. COVID-19 pandemic showed the importance of national vaccine production. In this context, Türkiye should act with a strategic planning towards supporting and prioritizing vaccine development studies and investments, increasing of numbers of vaccine production facilities and their capacities, and training qualified personnel and scientists to work in these institutions.

Anahtar Kelimeler

• COVID-19
• SARS-CoV-2
• vaccine

Kaynakça

1. Afkhami, S., D’Agostino, M. R., Zhang, A., Stacey, H. D., Marzok, A., Kang, A., … & Xing, Z. (2022). Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2. Cell, 185(5), 896-915.e19. https://doi.org/10.1016/j.cell.2022.02.005.
2. Ali, K., Berman, G., Zhou, H., Deng, W., Faughnan, V., Coronado-Voges, M., … & McPhee, R. (2021). Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. New England Journal of Medicine, 385(24),2241–2251. https://doi.org/10.1056/nejmoa2109522.
3. Alter, G., Yu, J., Liu, J., Chandrashekar, A., Borducchi, E. N., Tostanoski, L.H., … & Barouch, D. H. (2021). Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature, 596(7871), 268–272. https://doi.org/10.1038/s41586-021-03681-2.
4. An, Y., Li, S., Jin, X., Han, J., Xu, K., Xu, S., … & Gao, G. F. (2022). A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates. Emerging Microbes & Infections, 11(1), 1058–1071. https://doi.org/10.1080/22221751.2022.2056524.
5. Ardicli, O., Azkur, A.K., & Azkur, D. (2022). A potential immunological silver bullet for COVID‐19: The trivalent chimpanzee adenoviral serotype‐68 vector (Tri:ChAd). Allergy, 77(8), 2565-2567. https://doi.org/10.1111/all.15333.
6. Azkur, A. (2020). COVID-19 ve hayvanlar. Veteriner Farmakoloji ve Toksikoloji Derneği Bülteni, 11(2), 49–60. https://doi.org/10.38137/vetfarmatoksbulten.768811.
7. Azkur, A.K., Akdis, M., Azkur, D., Sokolowska, M., van de Veen, W., Brüggen, M.C., … & Akdis, C.A. (2020b). Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy, 75(7), 1564-1581. doi: 10.1111/all.14364.
8. Azkur, D. & Azkur, A.K. (2020). COVID-19 hastalığının immünopatolojisi ve immünolojisindeki güncel veriler. Eurasian J Vet Sci, Covid-19 Special Issue, 65-75.

9. Baden, L.R., el Sahly, H.M., Essink, B., Kotloff, K., Frey, S., Novak, R., … & Zaks, T. (2021). Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. New England Journal of Medicine, 384(5), 403–416. https://doi.org/10.1056/nejmoa2035389.
10. Barouch, D.H., Stephenson, K.E., Sadoff, J., Yu, J., Chang, A., Gebre, M., … & Schuitemaker, H. (2021). Durable humoral and cellular immune responses 8 months after Ad26.COV2.S vaccination. New England Journal of Medicine, 385(10), 951–953. https://doi.org/10.1056/nejmc2108829.
11. Barros-Martins, J., Hammerschmidt, S. I., Cossmann, A., Odak, I., Stankov, M. v., Morillas Ramos, G., … & Behrens, G.M.N. (2021). Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nature Medicine, 27(9), 1525–1529. https://doi.org/10.1038/s41591-021-01449-9.
12. Behrens, G.M., Cossmann, A., Stankov, M.V., Nehlmeier, I., Kempf, A., Hoffmann, M. & Pöhlmann, S. (2021) SARS-CoV-2 delta variant neutralisation after heterologous ChAdOx1-S/BNT162b2 vaccination. Lancet, 398(10305):1041-1042. doi: 10.1016/S0140-6736(21)01891-2.
13. Bolat, Y. & Doymaz M.Z. (1998). Viral Hastalıklara Karşı Bağışıklık. Veteriner Viroloji. Ders notları, Elazığ.
14. Bravo, L., Smolenov, I., Han, H.H., Li, P., Hosain, R., Rockhold, F., … & Clemens, R. (2022). Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial. The Lancet, 399(10323),461–472. https://doi.org/10.1016/S0140-6736(22)00055-1.
15. Bricker, T.L., Darling, T.L., Hassan, A.O., Harastani, H.H., Soung, A., Jiang, X., … & Boon, A.C.M. (2021) A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters. Cell Rep, 36(3), 109400. doi: 10.1016/j.celrep.2021.109400.
16. Cao, C., Cai, Z., Xiao, X., Rao, J., Chen, J., Hu, N., … & Xue, Y. (2021). The architecture of the SARS-CoV-2 RNA genome inside virion. Nature Communications,12(1),3917. https://doi.org/10.1038/s41467-021-22785-x.
17. Collier, A.R.Y., McMahan, K., Yu, J., Tostanoski, L. H., Aguayo, R., Ansel, J., … & Barouch, D.H. (2021). Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA - Journal of the American Medical Association, 325(23), 2370–2380. https://doi.org/10.1001/jama.2021.7563.
18. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020) The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 5(4), 536-544. doi: 10.1038/s41564-020-0695-z.
19. Costa Clemens, S.A., Weckx, L., Clemens, R., Almeida Mendes, A.V., Ramos Souza, A., Silveira, M.B.V., … & de Arruda Cordeiro Matos, L.J. (2022). Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. The Lancet, 399(10324), 521–529. https://doi.org/10.1016/S0140-6736(22)00094-0.
20. Creech, C.B., Anderson, E., Berthaud, V., Yildirim, I., Atz, A.M., Melendez Baez, I., … & KidCOVE Study Group. (2022). Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2203315.
21. Dai, L., Gao, L., Tao, L., Hadinegoro, S.R., Erkin, M., Ying, Z., … & ZF2001 Global Trial Group. (2022). Efficacy and safety of the RBD-Dimerb Covid-19 vaccine ZF2001 in adults. The New England Journal of Medicine, 386(22), 2097-2111. https://doi.org/10.1056/NEJMoa2202261.
22. Du, Y., Xu, Y., Feng, J., Hu, L., Zhang, Y., Zhang, B., … & Peng, T. (2021). Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse. Vaccine, 39(16),2280–2287. https://doi.org/10.1016/j.vaccine.2021.03.006.
23. Dunkle, L.M., Kotloff, K.L., Gay, C. L., Áñez, G., Adelglass, J.M., Barrat Hernández, A.Q., … & Dubovsky, F. (2022). Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. New England Journal of Medicine, 386(6), 531–543. https://doi.org/10.1056/nejmoa2116185.
24. El Sahly, H.M., Baden, L.R., Essink, B., Doblecki-Lewis, S., Martin, J.M., Anderson, E.J., … & Miller, J. (2021). Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at completion of blinded phase. New England Journal of Medicine, 385(19), 1774–1785. https://doi.org/10.1056/nejmoa2113017.
25. Emary, K.R.W., Golubchik, T., Aley, P.K., Ariani, C. v., Angus, B., Bibi, S., … & Pollard, A.J. (2021). Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. The Lancet, 397(10282), 1351–1362. https://doi.org/10.1016/S0140-6736(21)00628-0.
26. Falsey, A.R., Sobieszczyk, M.E., Hirsch, I., Sproule, S., Robb, M.L., Corey, L., … & AstraZeneca AZD1222 Clinical Study Group. (2021) Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine. N Engl J Med, 385(25), 2348-2360. doi: 10.1056/NEJMoa2105290.
27. Frenck, R.W., Klein, N.P., Kitchin, N., Gurtman, A., Absalon, J., Lockhart, S., … & Gruber, W.C. (2021). Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. New England Journal of Medicine, 385(3), 239–250. https://doi.org/10.1056/nejmoa2107456.
28. Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., … & Qin, C. (2020) Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369(6499), 77-81. doi: 10.1126/science.abc1932.
29. Gao, Y. dong, Ding, M., Dong, X., Zhang, J. jin, Kursat Azkur, A., Azkur, D., … & Akdis, C.A. (2021). Risk factors for severe and critically ill COVID-19 patients: A review. Allergy: European Journal of Allergy and Clinical Immunology, Vol. 76, pp. 428–455. Blackwell Publishing Ltd. https://doi.org/10.1111/all.14657.
30. Gilbert, P.B., Montefiori, D.C., McDermott, A.B., Fong, Y., Benkeser, D., Deng, W., … & Koup, R. A. (2022). Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science,375(6576),43-50. doi:10.1126/science.abm3425.
31. Hassan, A.O., Kafai, N.M., Dmitriev, I.P., Fox, J. M.,Smith, B.K., Harvey, I.B., … & Diamond, M.S. (2020). A single-dose intranasal chad vaccine protects upper and lower respiratory tracts against SARS-CoV-2. cell, 183(1), 169-184.e13. https://doi.org/10.1016/j.cell.2020.08.026.
32. Hassan, A.O., Feldmann, F., Zhao, H., Curiel, D.T., Okumura, A., Tang-Huau, T.L., … & Diamond, M.S. (2021b) A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Rep Med, 2(4),100230. doi: 10.1016/j.xcrm.2021.
33. Hassan, A.O., Shrihari, S., Gorman, M.J., Ying, B., Yaun, D., Raju, S., … & Diamond, M.S. (2021a) An intranasal vaccine durably protects against SARS-CoV-2 variants in mice. Cell Rep, 36(4),109452. doi: 10.1016/j.celrep.2021.109452.
34. Heath, P.T., Galiza, E.P., Baxter, D.N., Boffito, M., Browne, D., Burns, F., … & Toback, S. (2021). Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. New England Journal of Medicine, 385(13), 1172–1183. https://doi.org/10.1056/nejmoa2107659.
35. Hollstein, M.M., Münsterkötter, L., Schön, M.P., Bergmann, A., Husar, T.M., Abratis, A., … & Erpenbeck, L. (2022a). Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination. Allergy. Aug;77(8), 2381-2392. doi: 10.1111/all.15247
36. Hollstein, M.M., Münsterkötter, L., Schön, M.P., Bergmann, A., Husar, T.M., Abratis, A., … & Erpenbeck, L. (2022b). Long-term effects of homologous and heterologous SARS-CoV-2 vaccination on humoral and cellular immune responses. Allergy. May 25, 10.1111/all.15373. doi: 10.1111/all.15373.
37. Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., … & Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5.
38. ICTV (2021) Virus Taxonomy: 2021 Release. https://talk.ictvonline.org/taxonomy/
39. Ikegame, S., Siddiquey, M.N.A., Hung, C.T., Haas, G., Brambilla, L., Oguntuyo, K.Y., … & Lee, B. (2021). Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants. Nature Communications,12(1),4598. https://doi.org/10.1038/s41467-021-24909-9.
40. Jara, A., Undurraga, E.A., González, C., Paredes, F., Fontecilla, T., Jara, G., … & Araos, R. (2021). Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. New England Journal of Medicine, 385(10), 875–884. https://doi.org/10.1056/nejmoa2107715.
41. Jara, A., Undurraga, E.A., Zubizarreta, J.R., González, C., Pizarro, A., Acevedo, J., … & Araos, R. (2022). Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine: a large-scale prospective cohort study. The Lancet Global Health, 10(6), e798–e806. https://doi.org/10.1016/S2214-109X(22)00112-7.
42. Johnson, A.G., Amin, A.B., Ali, A.R., Hoots, Brooke, Cadwell, B. L., Arora, S., … & Scobie, H.M. (2022). COVID-19 incidence and death rates among unvaccinated and fully vaccinated adults with and without booster doses during periods of delta and omicron variant emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021. MMWR Morb Mortal Wkly Rep, 71(4),132-138. doi: 10.15585/mmwr.mm7104e2.
43. Kuloğlu, Z.E., El, R., Guney-Esken, G., Tok, Y., Talay, Z.G., Barlas, T., … & Can, F. (2022) Effect of BTN162b2 and CoronaVac boosters on humoral and cellular immunity of individuals previously fully vaccinated with CoronaVac against SARS-CoV-2: A longitudinal study. Allergy, 77(8), 2459-2467. 10.1111/all.15316.
44. Li, J., Hou, L., Guo, X., Jin, P., Wu, S., Zhu, J., … & Zhu, F. (2022). Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: a randomized phase 4 trial. Nature Medicine,28(2),401–409. https://doi.org/10.1038/s41591-021-01677-z.
45. Liang, J. G., Su, D., Song, T. Z., Zeng, Y., Huang, W., Wu, J., … & Liang, P. (2021). S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Nature Communications,12(1),1346. https://doi.org/10.1038/s41467-021-21634-1.
46. Logunov, D.Y., Dolzhikova, I. v., Shcheblyakov, D. v., Tukhvatulin, A. I., Zubkova, O. v., Dzharullaeva, A.S., … & Gintsburg, A.L. (2021). Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. The Lancet, 397(10275), 671–681. https://doi.org/10.1016/S0140-6736(21)00234-8.
47. Lopez Bernal, J., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., … & Ramsay, M. (2021) Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med, 385(7):585-594. doi: 10.1056/NEJMoa2108891.
48. Lu, L., Mok, B.W.-Y., Chen, L.-L., Chan, J.M.-C., Tsang, O.T.-Y., Lam, B.H.-S., … & To, K.K.-W. (2021). Neutralization of severe acute respiratory syndrome coronavirus 2 omicron variant by sera from bnt162b2 or coronavac vaccine recipients. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab1041.
49. Madhi, S.A., Baillie, V., Cutland, C.L., Voysey, M., Koen, A.L., Fairlie, L., … & Izu, A. (2021). Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. New England Journal of Medicine, 384(20), 1885–1898. https://doi.org/10.1056/nejmoa2102214.
50. Melo-González, F., Soto, J.A., González, L.A., Fernández, J., Duarte, L.F., Schultz, B.M., … & Bueno, S. M. (2021). Recognition of variants of concern by antibodies and t cells induced by a SARS-CoV-2 inactivated vaccine. Frontiers in Immunology, Nov9(12),747830. doi:https://doi.org/10.3389/fimmu.2021.747830.
51. Moeller, N.H., Shi, K., Demir, Ö., Belica, C., Banerjee, S., Yin, L., Durfee, C., Amaro, R.E. & Aihara, H. (2022) Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN. Proc Natl Acad Sci USA, 119(9):e2106379119. doi: 10.1073/pnas.2106379119.
52. Nordström, P., Ballin, M., & Nordström, A. (2022). Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden. The Lancet, 399(10327), 814–823. https://doi.org/10.1016/S0140-6736(22)00089-7.
53. Pavel, S.T.I., Yetiskin, H., Uygut, M.A., Aslan, A.F., Aydın, G., İnan, Ö., … & Ozdarendeli, A. (2021). Development of an inactivated vaccine against SARS CoV-2. Vaccines, 9(11), 1266. https://doi.org/10.3390/vaccines9111266.
54. Pérez-Then, E., Lucas, C., Monteiro, V.S., Miric, M., Brache, V., Cochon, L., … & Iwasaki, A. (2022). Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nature Medicine, 28(3), 481–485. https://doi.org/10.1038/s41591-022-01705-6.
55. Poh, X.Y., Tan, C.W., Lee, I.R., Chavatte, J.M., Fong, S.W., Prince, T., … & Young, B.E. (2022) Antibody response of heterologous vs homologous mRNA vaccine boosters against the SARS-CoV-2 Omicron variant: interim results from the PRIBIVAC study, A Randomized Clinical Trial. Clin Infect Dis, ciac345. doi: 10.1093/cid/ciac345.
56. Polack, F.P., Thomas, S.J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., … & Gruber, W.C. (2020). Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine, 383(27),2603–2615. https://doi.org/10.1056/nejmoa2034577.
57. Pollard, A.J. & Bijker, E.M. (2021) A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol, 21(2),83-100. doi: 10.1038/s41577-020-00479-7.
58. Sadoff, J., Gray, G., Vandebosch, A., Cárdenas, V., Shukarev, G., Grinsztejn, B., … & Douoguih, M. (2022). Final analysis of efficacy and safety of single-dose Ad26.COV2.S. New England Journal of Medicine, 386(9), 847–860. https://doi.org/10.1056/nejmoa2117608.
59. Sasaki, M., Uemura, K., Sato, A., Toba, S., Sanaki, T., Maenaka, K., … & Sawa, H. (2021). SARS-CoV-2 variants with mutations at the S1/ S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells. PLoS Pathogens, 17(1). https://doi.org/10.1371/journal.ppat.1009233.
60. Schmidt, T., Klemis, V., Schub, D., Mihm, J., Hielscher, F., Marx, S., … & Sester, M. (2021). Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nature Medicine,27(9),1530–1535. https://doi.org/10.1038/s41591-021-01464-w.
61. Shi, J., Wen, Z., Zhong, G., Yang, H., Wang, C., Huang, B., … & Bu, Z. (2020) Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science, 368(6494),1016-1020. doi: 10.1126/science.abb7015.
62. Stephenson, K.E., le Gars, M., Sadoff, J., de Groot, A. M., Heerwegh, D., Truyers, C., … & Barouch, D. H. (2021). Immunogenicity of the Ad26.COV2.S vaccine for COVID-19. JAMA - Journal of the American Medical Association, 325(15), 1535–1544. https://doi.org/10.1001/jama.2021.3645.
63. Stuart, A.S.V., Shaw, R.H., Liu, X., Greenland, M., Aley, P.K., Andrews, N.J., … & Snape, M.D. (2022). Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial. The Lancet,399(10319),36–49. https://doi.org/10.1016/S0140-6736(21)02718-5.
64. Tanriover, M.D., Doğanay, H.L., Akova, M., Güner, H. R., Azap, A., Akhan, S., … & Aksu, K. (2021). Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. The Lancet, 398(10296), 213–222. https://doi.org/10.1016/S0140-6736(21)01429-X.
65. Tian, J.H., Patel, N., Haupt, R., Zhou, H., Weston, S., Hammond, H., … & Smith, G. (2021). SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nature Communications, 12(1). https://doi.org/10.1038/s41467-020-20653-8.
66. Toback, S., Galiza, E., Cosgrove, C., Galloway, J., Goodman, A.L., Swift, P.A., … & Fox, P. (2022). Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial. The Lancet Respiratory Medicine,10(2),167–179. https://doi.org/10.1016/S2213-2600(21)00409-4.
67. Van Doremalen, N., Purushotham, J.N., Schulz, J.E., Holbrook, M. G., Bushmaker, T., Carmody, A., … & Munster, V. J. (2021). Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models. Sci Transl Med, 13(607):eabh0755. doi: 10.1126/scitranslmed.abh0755.
68. Voysey, M., Clemens, S.A.C., Madhi, S.A., Weckx, L.Y., Folegatti, P.M., Aley, P.K., … & Oxford COVID Vaccine Trial Group. (2021) 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, 397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1.
69. Walter, E.B., Talaat, K.R., Sabharwal, C., Gurtman, A., Lockhart, S., Paulsen, G.C., … & C4591007 Clinical Trial Group. (2022) Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N Engl J Med, 386(1),35-46. doi: 10.1056/NEJMoa2116298.
70. Wanlapakorn, N., Suntronwong, N., Phowatthanasathian, H., Yorsaeng, R., Thongmee, T., Vichaiwattana, P., … & Poovorawan, Y. (2022). Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data. Vaccine, 40(23), 3203–3209. https://doi.org/10.1016/j.vaccine.2022.04.043.
71. WHO (2022a) Tracking SARS-CoV-2 variants. https://www.who.int/activities/tracking-SARS-CoV-2-variants
72. WHO (2022b) WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/
73. Wu, K., Werner, A.P., Moliva, J.I., Koch, M., Choi, A., Stewart-Jones, G.B.E., … & Edwards, D.K. (2021a) mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv, 2021.01.25.427948. doi: 10.1101/2021.01.25.427948.
74. Wu, S., Huang, J., Zhang, Z., Wu, J., Zhang, J., Hu, H., … & Chen, W. (2021b). Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial. The Lancet Infectious Diseases, 21(12), 1654–1664. https://doi.org/10.1016/S1473-3099(21)00396-0.
75. Wu, S., Zhong, G., Zhang, J., Shuai, L., Zhang, Z., Wen, Z., … & Chen, W. (2020). A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-17972-1.
76. Xu, F., Wu, S., Yi, L., Peng, S., Wang, F., Si, W., … & Zhu, T. (2022). Safety, mucosal and systemic immunopotency of an aerosolized adenovirus-vectored vaccine against SARS-CoV-2 in rhesus macaques. Emerg Microbes Infect, 11(1),438-441. doi: 10.1080/22221751.2022.2030199.
77. Ye, Z.-W., Ong, C. P., Tang, K., Fan, Y., Luo, C., Zhou, R., … & Jin, D.-Y. (2022). Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals. Cell Mol Immunol, 19(5),588-601. doi: 10.1038/s41423-022-00855-4.
78. Yu, J., Tostanoski, L. H., Mercado, N.B., McMahan, K., Liu, J., Jacob-Dolan, C., … & Barouch, D.H. (2021). Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques. Nature, 596(7872), 423–427. https://doi.org/10.1038/s41586-021-03732-8.
79. Zhang, L., Jackson, C.B., Mou, H., Ojha, A., Peng, H., Quinlan, B.D., … & Choe, H. (2020) SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun., 11(1),6013. doi: 10.1038/s41467-020-19808-4.
80. Zhang, R., Khong, K.W., Leung, K.Y., Liu, D., Fan, Y., Lu, L., … & Hung, I.F.N. (2021). Antibody response of BNT162b2 and coronavac platforms in recovered individuals previously infected by COVID-19 against SARS-CoV-2 wild type and delta variant. Vaccines,9(12). https://doi.org/10.3390/vaccines9121442.
81. Zhu, F.C., Guan, X.H., Li, Y.H., Huang, J.Y., Jiang, T., Hou, L.H., … & Chen, W. (2020b). Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet,396(10249),479–488. https://doi.org/10.1016/S0140-6736(20)31605-6.
82. Zhu, F.C., Li, Y.H., Guan, X.H., Hou, L.H., Wang, W.J., Li, J.X., … & Chen, W. (2020a). Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet, 395(10240), 1845–1854. https://doi.org/10.1016/S0140-6736(20)31208-3.
83. Zuo, F., Abolhassani, H., Du, L., Piralla, A., Bertoglio, F., de Campos-Mata, L., … & Pan-Hammarström, Q. (2022). Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant. Nature Communications,13(1),2670. https://doi.org/10.1038/s41467-022-30340-5.