Exploration of Immunology

From: Vaccine efficacy—the biggest challenge today

Table 1. Examples of vaccines developed against certain viruses.

Virus	Vaccine vector	Findings
HIV	MVA gag p24/p17	Phase I terminated: low immune responses [23]
HIV	VEE gag	Phase 1 terminated: stability issues, low immunity [24]
HIV	ALVAC-HIV	Safe, cellular & Ab responses in phase I [25]
HIV	AAV-bnAbs	Low Ab responses in phase I [29]
HIV	mRNA-LNPs	nAbs in 80% of vaccinees in phase I [30]
HIV	GT HIV gp120 NPs	Strong immune responses in phase I [31]
HPV	HPV-VLPs	Cervarix approved for cervical cancer [35]
HPV	HPV-VLPs	Gardasil, Gardasil 9 approved for cervical cancer [36, 37]
HPV	SFV-HPV E6/E7	Strong immune responses in all patients in phase I [40]
HPV	SFV-HPV E6/E7	Reduction in lesions in 94% of patients in phase II [41]
EBOV	VEE-GP/NP	Protection against EBOV in mice and guinea pigs [43]
EBOV	rVSV-ZEBOV	Excellent vaccine efficacy in phase III [44, 45]
EBOV	rVSV-ZEBOV	Approval by the FDA in 2019 [46]
EBOV	Ad26.ZEBOV/MVA	Robust humoral responses in phase II [47]
EBOV	Ad26.ZEBOV-GP	Approval by the EMA in 2020 [48]
IVA	LAIV	Approval by the FDA [52, 53]
IVA	Inactivated IVA	Approval of several vaccines [57]
IVA	Split-virion vaccine	Strong immune responses in phase IV [58, 59]
IVA	Split-virion vaccine	Approval of IIV3 and IIV4 vaccines [59]
IVA	Inflexal V virosomes	Good immunogenicity in clinical trials [63]
IVA	AdV-HA/M2e/NP	Strong immunogenicity, protection against IVA [65, 66]
IVA	PICV rP18tri	Strong immune responses, protection in mice [67, 68]
IVA	NDV-HA	Robust immune responses, protection in mice [69]
IVA	BEVS Flublok	Approval for vaccination against IVA and IVB [71]
IVA	MV-HA	Protection against IVA in cotton rats [72]
IVA	VSV-H5N1	Protection in mice against H5 clades 1 and 2 [73]
IVA	SFV-HA saRNA	90% protection in mice after 10 µg saRNA dose [74]
IVA	VEE-HA	80-86% Ab responses in phase I/II [75]
IVA	IVA-VLPs COBRA	Protection against multiple IVA subtypes [76]
IVA	HA mRNA	Strong immune responses in mice and macaques [77]
IVA	HA mRNA	Comparable Ab responses to control vaccine in phase I [78]
IVA	HA mRNA	Statistically superior to control vaccine in phase III [79]
COVID-19	CoronaVac (WV)	50.7% efficacy against symptomatic COVID-19 and 100% against hospitalization [12]
COVID-19	CoronaVac (WV)	EUA in 54 countries in 2021 [13]
COVID-19	BBIBP-CoV (WV)	78.1% vaccine efficacy in phase III [80]
COVID-19	BBIBP-CoV (WV)	EUA in China 2020, by the WHO in 2021 [81, 82]
COVID-19	COVAX-19 + Adj	Protection in hamster against SARS-CoV-2 [83]
COVID-19	COVAX-19 + Adj	Robust immune responses in phase II [84]
COVID-19	COVAX-19 + Adj	Reduced severity of COVID in phase III [85]
COVID-19	NVX-Cov2373 + Adj	Protection against SARS-CoV-2 in rats, baboons [86]
COVID-19	NVX-Cov2373 + Adj	Superior Ab responses to COVID-19 patient sera [87]
COVID-19	NVX-Cov2373 + Adj	76.1% efficacy against symptomatic COVID-19 and 100% against severe disease in phase III [88]
COVID-19	NVX-Cov2373 + Adj	CMA in the EU in 2020 and in the UK in 2021 [89]
COVID-19	ChAdOx1 nCoV-19	Protection against SARS-CoV-2 in macaques [90]
COVID-19	ChAdOx1 nCoV-19	62-90% vaccine efficacy in phase III [8]
COVID-19	ChAdOx1 nCoV-19	EUA in the UK in 2020 [9]
COVID-19	Ad5-nCoV	EUA in China in 2021 [91]
COVID-19	Ad26.COV2.S	52.9% vaccine efficacy in phase III [92]
COVID-19	Ad26.COV2.S	EUA by the FDA in 2021 [93]
COVID-19	Ad26-S/Ad5-S	91% vaccine efficacy in phase III [95]
COVID-19	Ad26-S/Ad5-S	EUA in Russia in 2020 [96]
COVID-19	VSV-SARS-CoV-2 S	Protection of mice against SARS-CoV-2 [97]
COVID-19	VSV-SARS-CoV-2 S	Low immunogenicity, termination of phase I trial [98]
COVID-19	VSV-∆G	Potent nAbs in golden Syrian Hamsters [99]
COVID-19	VSV-∆G	Robust nAb responses in phase II [100]
COVID-19	INO-4800 DNA	Robust Ab responses in mice and guinea pigs [101]
COVID-19	INO-4800 DNA	Superior Ab response after high dose booster in phase II [102]
COVID-19	ZyCoV-D DNA	nAbs in mice, guinea pigs and rabbits [103]
COVID-19	ZyCoV-D DNA	nAbs in phase I/II [104]
COVID-19	ZyCoV-D DNA	66.6% vaccine efficacy in phase III [10]
COVID-19	ZyCoV-D DNA	EUA granted in India in 2021 [11]
COVID-19	BNT162b2 RNA	Protection against SARS-CoV-2 in macaques [105]
COVID-19	BNT162b2 RNA	95% vaccine efficacy in phase III [5]
COVID-19	BNT162b2 RNA	EUA granted in the EU and Switzerland in 2020 [6]
COVID-19	mRNA-1273 RNA	Protection against SARS-CoV-2 in mice and primates [106]
COVID-19	mRNA-1273 RNA	94.1% vaccine efficacy in phase III [107]
COVID-19	mRNA-1273 RNA	EUA granted by the FDA in 2020 [108]
COVID-19	LNP-nCoVsaRNA	Ab responses in mice [109]
COVID-19	LNP-nCoVsaRNA	< 100% seroconversion in phase I [110]
COVID-19	LNP-nCoVsaRNA	Superior seroconversion after booster dose in phase II [111]
COVID-19	LUNAR-CoV RNA	Phase II: 95% protection against severe COVI-19 and 55% protection against symptomatic COVID-19 [112]
COVID-19	LION-VEECoV RNA	Safety and immunogenicity in phase II/III [113]
COVID-19	LION-VEECoV RNA	EUA granted in India in 2025 [114]

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AAV: adeno-associated virus; Ab: antibody; Ad26: adenovirus serotype 26; Adj: adjuvant; ALVAC: canarypox virus; BEVS: baculovirus expression vector system; bnAbs: broadly neutralizing antibodies; CMA: conditional marketing authorization; COBRA: computationally optimized broadly reactive antigen; COVID-19: Coronavirus disease 2019; EBOV: Ebola virus; EMA: European Medicines Agency; EUA: emergency use authorization; FDA: Food and Drug Administration; GP: glycoprotein; GT: germline targeting; HA: hemagglutinin; HIV: human immunodeficiency virus; HPV: human papillomavirus; IVA: influenza virus A; IVB: influenza virus B; LAIV: live attenuated influenza virus; LION: lipid inorganic nanoparticle; LNP: lipid nanoparticle; MV: measles virus; MVA: modified vaccinia Ankara; nAbs: neutralizing antibodies; NDV: Newcastle disease virus; NP: nucleoprotein; NPs: nanoparticles; PICV: Pichinde virus; S: spike; saRNA: self-amplifying RNA; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SFV: Semliki Forest virus; VEE: Venezuelan equine encephalitis virus; VLPs: virus-like particles; VSV: vesicular stomatitis virus; WV: whole virus; ZEBOV: Zaire Ebola virus.

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KL: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.

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The author declares that he has no conflicts of interest.

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References

Jenner’s Breakthrough [Internet]. Philadelphia: College of Physicians of Philadelphia; c2026 [cited 2026 Apr 20]. Available from: https://historyofvaccines.org/history/edward-jenner-frs-frcpe/timeline/

Lundstrom K. COVID-19 Vaccines: Where Did We Stand at the End of 2023? Viruses. 2024;16:203. [DOI] [PubMed] [PMC]

Amanna IJ, Slifka MK. Successful Vaccines. Curr Top Microbiol Immunol. 2020;428:1–30. [DOI] [PubMed] [PMC]

Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–27. [DOI] [PubMed]

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al.; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383:2603–15. [DOI] [PubMed] [PMC]

Lamb YN. BNT162b2 mRNA COVID-19 Vaccine: First Approval. Drugs. 2021;81:495–501. [DOI] [PubMed] [PMC]

FDA Approves First COVID-19 Vaccine [Internet]. [cited 2026 Apr 20]. Available from: http://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine

Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al.; Oxford COVID Vaccine Trial Group. 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. 2021;397:99–111. [DOI] [PubMed] [PMC]

GOV.UK. Regulatory Approval of COVID-19 Vaccine AstraZeneca [Internet]. [cited 2026 Apr 20]. Available from: http://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca

10.

Khobragade A, Bhate S, Ramaiah V, Deshpande S, Giri K, Phophle H, et al.; ZyCoV-D phase 3 Study Investigator Group. Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India. Lancet. 2022;399:1313–21. [DOI] [PubMed] [PMC]

11.

Mallapaty S. India’s DNA COVID vaccine is a world first - more are coming. Nature. 2021;597:161–2. [DOI] [PubMed]

12.

Palacios R, Patiño EG, de Oliveira Piorelli R, Conde MTRP, Batista AP, Zeng G, et al. Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac - PROFISCOV: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21:853. [DOI] [PubMed] [PMC]

13.

WHO validates Sinovac COVID-19 vaccine for emergency use and issues interim policy recommendations [Internet]. [cited 2026 Jan 9]. Available from: https://www.who.int/news/item/01-06-2021-who-validates-sinovac-covid-19-vaccine-for-emergency-use-and-issues-interim-policy-recommendations

14.

Suah JL, Husin M, Tok PSK, Tng BH, Thevananthan T, Low EV, et al. Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study. Int J Infect Dis. 2022;119:69–76. [DOI] [PubMed] [PMC]

15.

Gupta RK. Will SARS-CoV-2 variants of concern affect the promise of vaccines? Nat Rev Immunol. 2021;21:340–1. [DOI] [PubMed] [PMC]

16.

Kricorian K, Civen R, Equils O. COVID-19 vaccine hesitancy: misinformation and perceptions of vaccine safety. Hum Vaccin Immunother. 2022;18:1950504. [DOI] [PubMed] [PMC]

17.

UNAIDS. Fast track: Ending the AIDS epidemic by 2030 [Internet]. c2026 [cited 2026 Apr 20]. Available from: https://www.unaids.org/en/resources/documents/2014/fast_track

18.

Lee JH, Crotty S. HIV vaccinology: 2021 update. Semin Immunol. 2021;51:101470. [DOI] [PubMed] [PMC]

19.

Haynes BF, Wiehe K, Borrow P, Saunders KO, Korber B, Wagh K, et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat Rev Immunol. 2023;23:142–58. [DOI] [PubMed] [PMC]

20.

Stephenson KE, D’Couto HT, Barouch DH. New concepts in HIV-1 vaccine development. Curr Opin Immunol. 2016;41:39–46. [DOI] [PubMed] [PMC]

21.

Laher F, Bekker L, Garrett N, Lazarus EM, Gray GE. Review of preventative HIV vaccine clinical trials in South Africa. Arch Virol. 2020;165:2439–52. [DOI] [PubMed] [PMC]

22.

Shim I, Rogowski L, Venketaraman V. Progress and Recent Developments in HIV Vaccine Research. Vaccines (Basel). 2025;13:690. [DOI] [PubMed] [PMC]

23.

Peters BS, Jaoko W, Vardas E, Panayotakopoulos G, Fast P, Schmidt C, et al. Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity. Vaccine. 2007;25:2120–7. [DOI] [PubMed]

24.

Wecker M, Gilbert P, Russell N, Hural J, Allen M, Pensiero M, et al. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin Vaccine Immunol. 2012;19:1651–60. [DOI] [PubMed] [PMC]

25.

Gray GE, Huang Y, Grunenberg N, Laher F, Roux S, Andersen-Nissen E, et al. Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa. Sci Transl Med. 2019;11:eaax1880. [DOI] [PubMed] [PMC]

26.

Mdluli T, Jian N, Slike B, Paquin-Proulx D, Donofrio G, Alrubayyi A, et al. RV144 HIV-1 vaccination impacts post-infection antibody responses. PLoS Pathog. 2020;16:e1009101. [DOI] [PubMed] [PMC]

27.

Miller EP, Finkelstein MT, Erdman MC, Seth PC, Fera D. A Structural Update of Neutralizing Epitopes on the HIV Envelope, a Moving Target. Viruses. 2021;13:1774. [DOI] [PubMed] [PMC]

28.

Steinhardt JJ, Guenaga J, Turner HL, McKee K, Louder MK, O’Dell S, et al. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity. Nat Commun. 2018;9:877. [DOI] [PubMed] [PMC]

29.

Priddy FH, Lewis DJM, Gelderblom HC, Hassanin H, Streatfield C, LaBranche C, et al. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial. Lancet HIV. 2019;6:e230–9. [DOI] [PubMed] [PMC]

30.

Parks KR, Moodie Z, Allen MA, Yen C, Furch BD, MacPhee KJ, et al. Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial. Sci Transl Med. 2025;17:eady6831. [DOI] [PubMed] [PMC]

31.

Jardine J, Julien J, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013;340:711–6. [DOI] [PubMed] [PMC]

32.

Venkatesan P. Preliminary phase 1 results from an HIV vaccine candidate trial. Lancet Microbe. 2021;2:e95. [DOI] [PubMed]

33.

International AIDS Vaccine Initiative. A Phase 1 Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) [Internet]. [cited 2026 Apr 20]. Available from: http://www.clinicaltrials.gov/study/NCT05001373

34.

Markowitz LE, Schiller JT. Human Papillomavirus Vaccines. J Infect Dis. 2021;224:S367–78. [DOI] [PubMed] [PMC]

35.

Szarewski A. HPV vaccine: Cervarix. Expert Opin Biol Ther. 2010;10:477–87. [DOI] [PubMed]

36.

McLemore MR. Gardasil: Introducing the new human papillomavirus vaccine. Clin J Oncol Nurs. 2006;10:559–60. [DOI] [PubMed]

37.

Cuzick J. Gardasil 9 joins the fight against cervix cancer. Expert Rev Vaccines. 2015;14:1047–9. [DOI] [PubMed]

38.

Lin R, Jin H, Fu X. Comparative efficacy of human papillomavirus vaccines: systematic review and network meta-analysis. Expert Rev Vaccines. 2023;22:1168–78. [DOI] [PubMed]

39.

Daemen T, Riezebos-Brilman A, Bungener L, Regts J, Dontje B, Wilschut J. Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7. Vaccine. 2003;21:1082–8. [DOI] [PubMed]

40.

Komdeur FL, Singh A, van de Wall S, Meulenberg JJM, Boerma A, Hoogeboom BN, et al. First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers. Mol Ther. 2021;29:611–25. [DOI] [PubMed] [PMC]

41.

Eerkens AL, Esajas MD, Brummel K, Vledder A, van Rooij N, Plat A, et al. Vvax001, a Therapeutic Vaccine, for Patients with HPV16-Positive High-grade Cervical Intraepithelial Neoplasia: A Phase II Trial. Clin Cancer Res. 2025;31:1016–26. [DOI] [PubMed]

42.

Kuehn R, Ryan H, Okwaraeke KC, Gould S, Chaplin M, Riley M, et al. Vaccines for preventing Ebola virus disease. Cochrane Database Syst Rev. 2024;11:CD015828. [DOI] [PubMed] [PMC]

43.

Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, et al. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine. 2000;19:142–53. [DOI] [PubMed]

44.

Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015;386:857–66. [DOI] [PubMed]

45.

Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017;389:505–18. [DOI] [PubMed] [PMC]

46.

Saphire EO. A Vaccine against Ebola Virus. Cell. 2020;181:6. [DOI] [PubMed]

47.

Larivière Y, Matuvanga TZ, Osang’ir BI, Milolo S, Meta R, Kimbulu P, et al. Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomised, phase 2 trial. Lancet Infect Dis. 2024;24:746–59. [DOI] [PubMed]

48.

Zabdeno [Internet]. European Medicines Agency; c1995–2026 [cited 2026 Apr 20]. Available from: http://www.ema.europa.eu/en/medicines/human/EPAR/zabdeno

49.

Palese P. Making better influenza virus vaccines? Emerg Infect Dis. 2006;12:61–5. [DOI] [PubMed] [PMC]

50.

Chen J, Wang J, Zhang J, Ly H. Advances in Development and Application of Influenza Vaccines. Front Immunol. 2021;12:711997. [DOI] [PubMed] [PMC]

51.

Blanco-Lobo P, Nogales A, Rodríguez L, Martínez-Sobrido L. Novel Approaches for The Development of Live Attenuated Influenza Vaccines. Viruses. 2019;11:190. [DOI] [PubMed] [PMC]

52.

Wang P, Zheng M, Lau S, Chen P, Mok BW, Liu S, et al. Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines. mBio. 2019;10:e02180–19. [DOI] [PubMed] [PMC]

53.

Poehling KA, Caspard H, Peters TR, Belongia EA, Congeni B, Gaglani M, et al. 2015-2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children in the United States. Clin Infect Dis. 2018;66:665–72. [DOI] [PubMed] [PMC]

54.

Ainai A, Suzuki T, Tamura S, Hasegawa H. Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate. Viral Immunol. 2017;30:451–62. [DOI] [PubMed]

55.

Ainai A, van Riet E, Ito R, Ikeda K, Senchi K, Suzuki T, et al. Human immune responses elicited by an intranasal inactivated H5 influenza vaccine. Microbiol Immunol. 2020;64:313–25. [DOI] [PubMed] [PMC]

56.

Taaffe J, Zhong S, Goldin S, Rawlings KS, Cowling BJ, Zhang W. An overview of influenza H5 vaccines. Lancet Respir Med. 2025;13:e20–1. [DOI] [PubMed]

57.

Hu Y, Shao M, Hu Y, Liang Q, Jia N, Chu K, et al. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III clinical trial in children aged 6-35 months in China. Hum Vaccin Immunother. 2020;16:1691–8. [DOI] [PubMed] [PMC]

58.

Li S, Li L, Ai X, Yang L, Bai Y, Wang Z, et al. A randomized, controlled, blinded study of the safety, immunogenicity and batch consistency of Aleph inactivated split influenza vaccine made in China in Chinese people. Hum Vaccin Immunother. 2014;10:557–65. [DOI] [PubMed] [PMC]

59.

Influenza vaccine for 2020-2021. Med Lett Drugs Ther. 2020;62:145–50. [PubMed]

60.

Soema PC, Kompier R, Amorij J, Kersten GFA. Current and next generation influenza vaccines: Formulation and production strategies. Eur J Pharm Biopharm. 2015;94:251–63. [DOI] [PubMed]

61.

Glück R, Mischler R, Finkel B, Que JU, Scarpa B, Jr SJC. Immunogenicity of new virosome influenza vaccine in elderly people. Lancet. 1994;344:160–3. [DOI] [PubMed]

62.

Bovier PA. Epaxal: a virosomal vaccine to prevent hepatitis A infection. Expert Rev Vaccines. 2008;7:1141–50. [DOI] [PubMed]

63.

Herzog C, Hartmann K, Künzi V, Kürsteiner O, Mischler R, Lazar H, et al. Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine. 2009;27:4381–7. [DOI] [PubMed]

64.

Künzi V, Klap JM, Seiberling MK, Herzog C, Hartmann K, Kürsteiner O, et al. Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. Vaccine. 2009;27:3561–7. [DOI] [PubMed]

65.

Tutykhina I, Esmagambetov I, Bagaev A, Pichugin A, Lysenko A, Shcherbinin D, et al. Vaccination potential of B and T epitope-enriched NP and M2 against Influenza A viruses from different clades and hosts. PLoS One. 2018;13:e0191574. [DOI] [PubMed] [PMC]

66.

Hassan AO, Amen O, Sayedahmed EE, Vemula SV, Amoah S, York I, et al. Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses. PLoS One. 2017;12:e0186244. [DOI] [PubMed] [PMC]

67.

Dhanwani R, Ly H, Liang Y. Recombinant Tri-Segmented Pichinde Virus as a Novel Live Viral Vaccine Platform. Methods Mol Biol. 2017;1581:169–79. [DOI] [PubMed] [PMC]

68.

Dhanwani R, Zhou Y, Huang Q, Verma V, Dileepan M, Ly H, et al. A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose. J Virol. 2015;90:2551–60. [DOI] [PubMed] [PMC]

69.

Nakaya T, Cros J, Park MS, Nakaya Y, Zheng H, Sagrera A, et al. Recombinant Newcastle disease virus as a vaccine vector. J Virol. 2001;75:11868–73. [DOI] [PubMed] [PMC]

70.

Yang LPH. Recombinant trivalent influenza vaccine (flublok(®)): a review of its use in the prevention of seasonal influenza in adults. Drugs. 2013;73:1357–66. [DOI] [PubMed]

71.

Dunkle LM, Izikson R, Patriarca P, Goldenthal KL, Muse D, Callahan J, et al. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med. 2017;376:2427–36. [DOI] [PubMed]

72.

Ito T, Kumagai T, Yamaji Y, Sawada A, Nakayama T. Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein. Vaccines (Basel). 2020;8:149. [DOI] [PubMed] [PMC]

73.

Furuyama W, Reynolds P, Haddock E, Meade-White K, Le MQ, Kawaoka Y, et al. A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades. NPJ Vaccines. 2020;5:4. [DOI] [PubMed] [PMC]

74.

Fleeton MN, Chen M, Berglund P, Rhodes G, Parker SE, Murphy M, et al. Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. J Infect Dis. 2001;183:1395–8. [DOI] [PubMed]

75.

A Phase 1/2 Clinical Trial of an Alphavirus Replicon Vaccine for Influenza [Internet]. Blue Ash: Aprecia Pharmaceuticals, LLC.; c2018 [cited 2026 Apr 20]. Available from: http://www.clinicaltrials.gov/study/NCT00440362?tab=researcher

76.

Uno N, Ross TM. Multivalent next generation influenza virus vaccines protect against seasonal and pre-pandemic viruses. Sci Rep. 2024;14:1440. [DOI] [PubMed] [PMC]

77.

Hauguel T, Sharma A, Mastrocola E, Lowry S, Maddur MS, Hu CH, et al. Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines. NPJ Vaccines. 2024;9:183. [DOI] [PubMed] [PMC]

78.

Branche A, Mulligan MJ, Maniar A, Puente O, Oladipupo I, Crowther G, et al. A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults. Vaccines (Basel). 2025;13:383. [DOI] [PubMed] [PMC]

79.

Fitz-Patrick D, McVinnie DS, Jackson LA, Crowther G, Geevarughese A, Cannon KD, et al.; Pfizer C4781004 Trial Investigators. Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine. N Engl J Med. 2025;393:2001–11. [DOI] [PubMed]

80.

Kaabi NA, Zhang Y, Xia S, Yang Y, Qahtani MMA, Abdulrazzaq N, et al. Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. JAMA. 2021;326:35–45. [DOI] [PubMed] [PMC]

81.

Sinovac’s coronavirus vaccine candidate approved for emergency use in China-source [Internet]. Reuters; c2026 [cited 2026 Apr 20]. Available from: https://www.reuters.com/article/idUSKBN25O0Z0/

82.

Taylor A. WHO grants emergency use authorization for Chinese-made Sinopharm coronavirus vaccine [Internet]. The Washington Post; c1996–2026 [cited 2026 Apr 20]. Available from: https://www.washingtonpost.com/world/2021/05/07/who-sinopharm-emergency-use/

83.

Li L, Honda-Okubo Y, Baldwin J, Bowen R, Bielefeldt-Ohmann H, Petrovsky N. Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters. Vaccine. 2022;40:3182–92. [DOI] [PubMed] [PMC]

84.

Tabarsi P, Anjidani N, Shahpari R, Mardani M, Sabzvari A, Yazdani B, et al. Safety and immunogenicity of SpikoGen®, an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations. Clin Microbiol Infect. 2022;28:1263–71. [DOI] [PubMed] [PMC]

85.

Tabarsi P, Anjidani N, Shahpari R, Mardani M, Sabzvari A, Yazdani B, et al. Evaluating the efficacy and safety of SpikoGen®, an Advax-CpG55.2-adjuvanted severe acute respiratory syndrome coronavirus 2 spike protein vaccine: a phase 3 randomized placebo-controlled trial. Clin Microbiol Infect. 2023;29:215–20. [DOI] [PubMed] [PMC]

86.

Tian J, Patel N, Haupt R, Zhou H, Weston S, Hammond H, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021;12:372. [DOI] [PubMed] [PMC]

87.

Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020;383:2320–32. [DOI] [PubMed] [PMC]

88.

Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial. Clin Infect Dis. 2023;76:398–407. [DOI] [PubMed] [PMC]

89.

Parums DV. Editorial: First Approval of the Protein-Based Adjuvanted Nuvaxovid (NVX-CoV2373) Novavax Vaccine for SARS-CoV-2 Could Increase Vaccine Uptake and Provide Immune Protection from Viral Variants. Med Sci Monit. 2022;28:e936523. [DOI] [PubMed] [PMC]

90.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020;586:578–82. [DOI] [PubMed] [PMC]

91.

China approves two more domestic COVID-19 vaccines for public use [Internet]. Reuters; c2026 [cited 2026 Apr 20]. Available from: https://www.reuters.com/article/idUSKBN2AP1V8/

92.

Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al.; ENSEMBLE Study Group. Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. N Engl J Med. 2022;386:847–60. [DOI] [PubMed] [PMC]

93.

Emergency use authorization (EUA) of the janssen covid-19 vaccine to prevent coronavirus disease 2019 (COVID-19) [Internet]. Janssen Pharmaceutical Companies; c2021 [cited 2026 Apr 20]. Available from: http://www.fda.gov/media/146304/download

94.

Balakrishnan VS. The arrival of Sputnik V. Lancet Infect Dis. 2020;20:1128. [DOI] [PubMed] [PMC]

95.

Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al.; Gam-COVID-Vac Vaccine Trial Group. 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. Lancet. 2021;397:671–81. [DOI] [PubMed] [PMC]

96.

Callaway E. Russia’s fast-track coronavirus vaccine draws outrage over safety. Nature. 2020;584:334–5. [DOI] [PubMed]

97.

Case JB, Rothlauf PW, Chen RE, Kafai NM, Fox JM, Smith BK, et al. Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host Microbe. 2020;28:465–74.e4. [DOI] [PubMed] [PMC]

98.

Robbins JA, Tait D, Huang Q, Dubey S, Crumley T, Cote J, et al. Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial. EBioMedicine. 2022;82:104138. [DOI] [PubMed] [PMC]

99.

Yahalom-Ronen Y, Tamir H, Melamed S, Politi B, Shifman O, Achdout H, et al. A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge. Nat Commun. 2020;11:6402. [DOI] [PubMed] [PMC]

100.

Yahalom-Ronen Y, Erez N, Fisher M, Tamir H, Politi B, Achdout H, et al. Neutralization of SARS-CoV-2 Variants by rVSV-ΔG-Spike-Elicited Human Sera. Vaccines (Basel). 2022;10:291. [DOI] [PubMed] [PMC]

101.

Smith TRF, Patel A, Ramos S, Elwood D, Zhu X, Yan J, et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun. 2020;11:2601. [DOI] [PubMed] [PMC]

102.

Yao A, Jia S, Cheng X, Pan H, Wang Z, Yang H, et al. Immunogenicity and safety of a booster dose of the COVID-19 DNA vaccine in healthy adults aged 18 years and above: a single-center, randomized, observer-blind, placebo-controlled phase 2 trial. BMC Infect Dis. 2025;25:750. [DOI] [PubMed] [PMC]

103.

Dey A, Rajanathan TMC, Chandra H, Pericherla HPR, Kumar S, Choonia HS, et al. Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models. Vaccine. 2021;39:4108–16. [DOI] [PubMed] [PMC]

104.

Momin T, Kansagra K, Patel H, Sharma S, Sharma B, Patel J, et al. Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India. EClinicalMedicine. 2021;38:101020. [DOI] [PubMed] [PMC]

105.

Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M, et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature. 2021;592:283–9. [DOI] [PubMed]

106.

Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020;383:1544–55. [DOI] [PubMed] [PMC]

107.

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al.; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384:403–16. [DOI] [PubMed] [PMC]

108.

FDA Takes Additional Action in Fight against COVID-19 by Issuing Emergency Use Authorization for Second COVID-19 Vaccine [Internet]. Cision US Inc.; c2026 [cited 2026 Apr 20]. Available from: https://www.prnewswire.com/news-releases/fda-takes-additional-action-in-fight-against-covid-19-by-issuing-emergency-use-authorization-for-second-covid-19-vaccine-301196303.html

109.

McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat Commun. 2020;11:3523. [DOI] [PubMed] [PMC]

110.

Pollock KM, Cheeseman HM, Szubert AJ, Libri V, Boffito M, Owen D, et al.; COVAC1 study Group. Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial. EClinicalMedicine. 2022;44:101262. [DOI] [PubMed] [PMC]

111.

Szubert AJ, Pollock KM, Cheeseman HM, Alagaratnam J, Bern H, Bird O, et al. COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2. EClinicalMedicine. 2023;56:101823. [DOI] [PubMed] [PMC]

112.

Important Announcement [Internet]. William Reed Ltd.; c2025 [cited 2026 Apr 20]. Available from: http://www.biopharma-reporter.com

113.

GEMCOVAC^® mRNA Vaccines for COVID-19 [Internet]. Gennova Biopharmaceuticals Limited; c2006–2025 [cited 2026 Apr 20]. Available from: https://gennova.bio/gemcovac-19-2/

114.

HDT bio receives emergency use approval for covid-19 vaccine in India [Internet]. GlobalData Plc.; c2026 [cited 2026 Apr 21]. Available from: https://www.pharmaceutical-technology.com/news/hdt-bio-vaccine-india-approval/

115.

Ray GT, Lewis N, Klein NP, Daley MF, Wang SV, Kulldorff M, et al. Intraseason Waning of Influenza Vaccine Effectiveness. Clin Infect Dis. 2019;68:1623–30. [DOI] [PubMed] [PMC]

116.

Tokars JI, Patel MM, Foppa IM, Reed C, Fry AM, Ferdinands JM. Waning of Measured Influenza Vaccine Effectiveness Over Time: The Potential Contribution of Leaky Vaccine Effect. Clin Infect Dis. 2020;71:e633–41. [DOI] [PubMed] [PMC]

117.

Lewnard JA, Grad YH. Vaccine waning and mumps re-emergence in the United States. Sci Transl Med. 2018;10:eaao5945. [DOI] [PubMed] [PMC]

118.

Nikas A, Ahmed H, Zarnitsyna VI. Estimating Waning of Vaccine Effectiveness: A Simulation Study. Clin Infect Dis. 2023;76:479–86. [DOI] [PubMed] [PMC]

119.

Lim SY, Kim JY, Jung J, Yun S, Kim S. Waning of humoral immunity depending on the types of COVID-19 vaccine. Infect Dis (Lond). 2023;55:216–20. [DOI] [PubMed]

120.

Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399:924–44. [DOI] [PubMed] [PMC]

121.

DeDiego ML, Chiem K, Topham DJ. Directed selection of amino acid changes in the influenza hemagglutinin and neuraminidase affecting protein antigenicity. Vaccine. 2018;36:6383–92. [DOI] [PubMed]

122.

Papageorgiou AC, Mohsin I. The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies. Cells. 2020;9:2343. [DOI] [PubMed] [PMC]

123.

Choi JY, Smith DM. SARS-CoV-2 Variants of Concern. Yonsei Med J. 2021;62:961–8. [DOI] [PubMed] [PMC]

124.

Taucher C, Lazarus R, Dellago H, Maurer G, Weisova P, Corbic-Ramljak I, et al.; Valneva Phase 3 Booster Trial Group. Safety and immunogenicity against ancestral, Delta and Omicron virus variants following a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001): Interim analysis of an open-label extension of the randomized, controlled, phase 3 COV-COMPARE trial. J Infect. 2023;87:242–54. [DOI] [PubMed]

125.

Nawaz S, Janiad S, Fatima A, Saleem M, Fatima U, Ali A. Rapidly Evolving SARS-CoV-2: A Brief Review Regarding the Variants and their Effects on Vaccine Efficacies. Infect Disord Drug Targets. 2024;24:58–66. [DOI] [PubMed]

126.

de Bruyn G, Wang J, Purvis A, Ruiz MS, Adhikarla H, Alvi S, et al. Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study. EClinicalMedicine. 2023;62:102109. [DOI] [PubMed] [PMC]

127.

Tran TNM, May BP, Ung TT, Nguyen MK, Nguyen TTT, Dinh VL, et al. Preclinical Immune Response and Safety Evaluation of the Protein Subunit Vaccine Nanocovax for COVID-19. Front Immunol. 2021;12:766112. [DOI] [PubMed] [PMC]

128.

Lyke KE, Atmar RL, Islas CD, Posavad CM, Deming ME, Branche AR, et al.; DMID 21-0012 Study Group. Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants. NPJ Vaccines. 2023;8:98. [DOI] [PubMed] [PMC]

129.

Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, et al.; Wits-VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021;384:1885–98. [DOI] [PubMed] [PMC]

130.

Eyre DW, Taylor D, Purver M, Chapman D, Fowler T, Pouwels KB, et al. Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants. N Engl J Med. 2022;386:744–56. [DOI] [PubMed] [PMC]

131.

Alter G, Yu J, Liu J, Chandrashekar A, Borducchi EN, Tostanoski LH, et al. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature. 2021;596:268–72. [DOI] [PubMed] [PMC]

132.

Polinski JM, Weckstein AR, Batech M, Kabelac C, Kamath T, Harvey R, et al. Durability of the Single-Dose Ad26.COV2.S Vaccine in the Prevention of COVID-19 Infections and Hospitalizations in the US Before and During the Delta Variant Surge. JAMA Netw Open. 2022;5:e222959. [DOI] [PubMed] [PMC]

133.

Andrade VM, Christensen-Quick A, Agnes J, Tur J, Reed C, Kalia R, et al. INO-4800 DNA vaccine induces neutralizing antibodies and T cell activity against global SARS-CoV-2 variants. NPJ Vaccines. 2021;6:121. [DOI] [PubMed] [PMC]

134.

Walters JN, Schouest B, Patel A, Reuschel EL, Schultheis K, Parzych E, et al. Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates. Vaccine. 2022;40:2960–9. [DOI] [PubMed] [PMC]

135.

Martínez-Baz I, Trobajo-Sanmartín C, Miqueleiz A, Guevara M, Fernández-Huerta M, Burgui C, et al.; Investigators; other members of the Working Group for the Study of COVID-19 in Navarre. Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts, Navarre, Spain, April to August 2021. Euro Surveill. 2021;26:2100894. [DOI] [PubMed] [PMC]

136.

Sheikh A, Robertson C, Taylor B. BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant. N Engl J Med. 2021;385:2195–7. [PMID: 34670038 PMCID: PMC8552534 DOI: 10.1056/NEJMc2113864].

137.

Regev-Yochay G, Gonen T, Gilboa M, Mandelboim M, Indenbaum V, Amit S, et al. Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron. N Engl J Med. 2022;386:1377–80. [DOI] [PubMed] [PMC]

138.

Abu-Raddad LJ, Chemaitelly H, Ayoub HH, AlMukdad S, Yassine HM, Al-Khatib HA, et al. Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar. N Engl J Med. 2022;386:1804–16. [DOI] [PubMed] [PMC]

139.

Choi A, Koch M, Wu K, Dixon G, Oestreicher J, Legault H, et al. Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants. J Virol. 2021;95:e0131321. [DOI] [PubMed] [PMC]

140.

Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med. 2022;387:1279–91. [DOI] [PubMed] [PMC]

141.

Wang Q, Guo Y, Bowen A, Mellis IA, Valdez R, Gherasim C, et al. XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1. Cell Host Microbe. 2024;32:315–21.e3. [DOI] [PubMed] [PMC]

142.

Frise R, Baillon L, Zhou J, Kugathasan R, Peacock TP, Brown JC, et al. A self-amplifying RNA vaccine protects against SARS-CoV-2 (D614G) and Alpha variant of concern (B.1.1.7) in a transmission-challenge hamster model. Vaccine. 2022;40:2848–55. [DOI] [PubMed] [PMC]

143.

Kiang MV, Bubar KM, Maldonado Y, Hotez PJ, Lo NC. Modeling Reemergence of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination in the US. JAMA. 2025;333:2176–87. [DOI] [PubMed] [PMC]

144.

Faizan A, Rehman T, Mughal S. Re-emergence of polio in Pakistan: Can the nation achieve the WPV1 eradication goal? Health Sci Rep. 2024;7:e1862. [DOI] [PubMed] [PMC]

145.

Hromić-Jahjefendić A, Barh D, Uversky V, Aljabali AA, Tambuwala MM, Alzahrani KJ, et al. Can COVID-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading to? Vaccines (Basel). 2023;11:208. [DOI] [PubMed] [PMC]

146.

Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, et al. Direct gene transfer into mouse muscle in vivo. Science. 1990;247:1465–8. [DOI] [PubMed]

147.

COVID-19 vaccination, World [Internet]. WHO; c2024 [cited 2026 Apr 20]. Available from: https://data.who.int/dashboards/covid19/vaccines

148.

Yasmin F, Najeeb H, Moeed A, Naeem U, Asghar MS, Chughtai NU, et al. COVID-19 Vaccine Hesitancy in the United States: A Systematic Review. Front Public Health. 2021;9:770985. [DOI] [PubMed] [PMC]

149.

Wu J, Li Q, Tarimo CS, Wang M, Gu J, Wei W, et al. COVID-19 Vaccine Hesitancy Among Chinese Population: A Large-Scale National Study. Front Immunol. 2021;12:781161. [DOI] [PubMed] [PMC]

150.

Willis DE, Presley J, Williams M, Zaller N, McElfish PA. COVID-19 vaccine hesitancy among youth. Hum Vaccin Immunother. 2021;17:5013–5. [DOI] [PubMed] [PMC]

151.

Biswas N, Mustapha T, Khubchandani J, Price JH. The Nature and Extent of COVID-19 Vaccination Hesitancy in Healthcare Workers. J Community Health. 2021;46:1244–51. [DOI] [PubMed] [PMC]

152.

Ebrahimi OV, Johnson MS, Ebling S, Amundsen OM, Halsøy Ø, Hoffart A, et al. Risk, Trust, and Flawed Assumptions: Vaccine Hesitancy During the COVID-19 Pandemic. Front Public Health. 2021;9:700213. [DOI] [PubMed] [PMC]

153.

Storey D. COVID-19 Vaccine Hesitancy. Glob Health Sci Pract. 2022;10:e2200043. [DOI] [PubMed] [PMC]

154.

Lunn PD, Timmons S. Public misperceptions of COVID-19 vaccine effectiveness and waning: experimental evidence from Ireland. Public Health. 2023;214:81–4. [DOI] [PubMed] [PMC]

155.

Lundstrom K. Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents. Viruses. 2024;16:1762. [DOI] [PubMed] [PMC]

156.

Yan S, Luo Y, Zhan N, Xu H, Yao Y, Liu X, et al. Intranasal delivery of a recombinant adenovirus vaccine encoding the PEDV COE elicits potent mucosal and systemic antibody responses in mice. Microbiol Spectr. 2024;12:e0069224. [DOI] [PubMed] [PMC]

157.

Jung HE, Ku KB, Kang BH, Park JH, Kim HC, Kim K, et al. Intranasal delivery of an adenovirus-vector vaccine co-expressing a modified spike protein and a genetic adjuvant confers lasting mucosal immunity against SARS-CoV-2. Antiviral Res. 2023;216:105656. [DOI] [PubMed] [PMC]

158.

Komissarov AA, Dolzhikova IV, Efimov GA, Logunov DY, Mityaeva O, Molodtsov IA, et al. Boosting of the SARS-CoV-2-Specific Immune Response after Vaccination with Single-Dose Sputnik Light Vaccine. J Immunol. 2022;208:1139–45. [DOI] [PubMed] [PMC]

159.

Bathula NV, Friesen JJ, Casmil IC, Wayne CJ, Liao S, Soriano SKV, et al. Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity. J Control Release. 2024;374:28–38. [DOI] [PubMed]

160.

Jennewein MF, Schultz MD, Beaver S, Battisti P, Bakken J, Hanson D, et al. Intranasal replicon SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission. Mol Ther. 2025;33:3286–306. [DOI] [PubMed] [PMC]

161.

Coleman HJ, Rauch A, Langsfeld E, Anderson K, Parlikar U, Funke HH, et al. Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposit ion. J Pharm Sci. 2026;115:104066. [DOI] [PubMed] [PMC]