The Development of mRNA Vaccines for Infectious Diseases: Recent Updates

Figures & data

Figure 1 The mechanisms of mRNA vaccine. (A) mRNA vaccine in lipid nanoparticle when released in the body is translated to protein which then elicits immune response. (B) Self amplifying mRNA is released into the body and then complexed with RdRp which is then translated into protein and elicits immune response. (C) mRNA vaccine elicits immune response as the protein is expressed and recognized by CD4+ T helper cells; this activates CD8+ T and B cells. B cells produce neutralizing antibodies and memory B cells retain the memory for any subsequent infection. CD8+ T cells attack virus-infected cells. Created with BioRender.com.

Table 1 mRNA Vaccines Against Infectious Diseases

Disease	Vaccine/Funding Source	Dose Regimen	Phase	Outcome/Efficacy	Platform	References
SARS-CoV-2	BNT162b2, Pfizer-BioNTech	Two-dose regimen, 21 days apart, delivered in the deltoid muscle	Approved	95% (95% CI, 90.3 to 97.6)	LNP- encapsulated full-length spike mRNA	[^Citation69]
SARS-CoV-2	mRNA-1273, Moderna	Two-dose regimen, 21 days apart, delivered in the deltoid muscle	Approved	94.1% (95% CI, 89.3 to 96.8%)	LNP- encapsulated full-length spike mRNA	[^Citation88]
SARS-CoV-2	CV2nCoV/CVnCoV, CureVac AG	Two-dose regimen, 21 days apart, delivered intramuscularly	Preclinical	N/A	LNP- encapsulated sequence optimized spike mRNA	[^Citation140]
SARS-CoV-2	ARCoV, Walvax Biotechnology, PLA	Two-dose regimen, 28 days apart, delivered intramuscularly	Phase III	N/A	LNP- encapsulated full-length RBD mRNA	NCT4847102
Rabies	CV7201, CureVac AG	Three-dose regimen, delivered intradermally or intramuscularly	Phase I	GMT of 0·73 IU/mL (95% CI 0·36–1·46)	LNP- encapsulated full-length RABV-G mRNA	[^Citation96]
Rabies	CV7202, CureVac AG	Three-dose regimen, delivered intramuscularly	Phase I	GMTs of 4186 U/mL (13,253–88,185) and 20,707 U/mL (5592–76,678) for 1 and 2 μg groups	LNP- encapsulated full-length RABV-G mRNA	NCT3713086 [^Citation95]
Influenza	mRNA-H10N8, mRNA-H7N9, Moderna	Two-dose regimen, delivered intramuscularly	Phase I	For H10N8 HAI GMT was 13.9, for H7N9 HAI GMT was 13.6	LNP- encapsulated full-length HA glycoprotein mRNA from the H10N8 and H7N9 strain	[^Citation104]
Respiratory syncytial virus (RSV)	mRNA-1345, Moderna	Three-dose regimen, delivered intramuscularly	Phase I	GMF of 20.5 for RSV-A and GMF of 11.7 for RSV-B for young adults, GMF of 14.2 for RSV-A and GMF of 10.1 for RSV-B for older adults	LNP- encapsulated prefusion F protein	ModernaTx NCT4528719
Human metapneumovirus (HMPV) and parainfluenza virus type 3 (PIV3)	mRNA-1653, Moderna	Three dose regimen, delivered intramuscularly	Phase Ib	GMT of 6.04 for HMPV-A, 6.33 for HMPV-B and 3.24 for PIV3	LNP- encapsulated F protein coding mRNA from hMPV and PIV3	ModernaTx NCT4144348 NCT3392389
Human cytomegalovirus (HCMV)	mRNA-1647, Moderna	Three-dose regimen, delivered intramuscularly	Phase III	GMRs of 13.4–40.8	LNP- encapsulated six mRNAs coding the HCMV pentamer complex and gB antigens (UL128, UL 130, UL131, gB, gH, gL)	ModernaTx NCT5085366
Zika virus	mRNA-1893, Moderna	Two-dose regimen, delivered intramuscularly	Phase II	GMT of 1415 post dose two	LNP- encapsulated prME structural protein coding mRNA	ModernaTx NCT4917861
Epstein–Barr virus (EBV)	mRNA-1189, mRNA-1195 Moderna	N/A	Preclinical	10^3 and 10^5, B-cell and epithelial neutralization titers in mice	LNP- encapsulated four mRNAs coding the EBV glycoproteins (gp42, gp220, gH, gL)	ModernaTx
Human immunodeficiency virus (HIV)	HIV SAM, Env/MF59 and HIV-VRP vaccines, Biomedical Primate Research Centre, Rijswijk, The Netherlands	Three-dose regimen, delivered intramuscularly	Preclinical	GMTs of 10^6.14, 10^6.25, and 10^4.79 for Env/MF59, HIV SAM, and HIV-VRP respectively in rhesus macaques	Cationic nanoemulsion encoding HIV-1 TV1 Env gp140, HIV-1 TV1 Env gp140, HIV-1 TV1 Env gp140 protein with MF59	[^Citation24]
Human immunodeficiency virus (HIV)	HIV-1 antigen Gag vaccine, Virology Unit, Institute of Tropical Medicine, Antwerp, Belgium	Subcutaneous immunization of Balb/c mice	Preclinical	Secretion of type I interferon (IFN) and the recruitment of monocytes to the draining lymph nodes	HIV-1 antigen Gag complexed with the cationic lipid DOTAP/DOPE	[^Citation50]
Streptococcus	SAM vaccine, GlaxoSmithKline	Intramuscular immunization of CD-1 mice	Preclinical	GMT ratio of 10.55 and 0.17 for SLOdm and GMT ratio of 39.14 and 0.13 for BP-2a	Cationic nanoemulsion (CNE)-SAM expressing bacterial antigens. GAS Streptolysin-O (SLOdm) and the GBS pilus 2a backbone protein (BP-2a))	[^Citation37]

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