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. Author manuscript; available in PMC: 2023 Jan 27.
Published in final edited form as: Nanoscale. 2022 Jan 27;14(4):1054–1074. doi: 10.1039/d1nr03831a

Table 1.

Representative SARS-CoV-2 vaccines based on protein nanoparticles and lipid nanoparticles

Vaccine name Target Animals/ humans Ab responses and neutralizing Abs Cellular and other responses Protection and/or potential side effects Ref.

Nanoparticle-based SARS-CoV-2 vaccines
RBD-NP RBD Mice NHPs Induced SARS-CoV-2 S-specific Abs, with neutralizing Ab titers being 10-fold higher than a stabilized S protein against SARS-CoV-2 WT infection; neutralized SARS-CoV-2 B.1.1.7 variant Elicited SARS-CoV-2 RBD-specific CD4+ T cell responses Protected NHPs against SARS-CoV-2 infection 72 and 73
VLP-RBD RBD Mice Induced long-term RBD-specific Abs with neutralizing activity against live SARS-CoV-2 and pseudotyped SARS-CoV-2 WT and B.1.1.7, B.1.351, and P.1 variants, SARS-CoV-1, and SARS-related bat CoVs N/A Protected BALB/c mice against mouse-adapted SARS-CoV-2 challenge, with reduced clinical signs and pathological changes 37
RBD-SpyVLP RBD-mi3 RBD Mice Pigs Induced SARS-CoV-2 RBDspecific Abs and neutralizing Abs against pseudotyped and/or live SARS-CoV-2 infection Elicited SARS-CoV-2 RBD-specific B-cell responses and weak T-cell responses N/A 74 and 75
RBD-ferritin S2GΔHR2 RBD S Mice NHPs Induced SARS-CoV-2 S/RBDspecific Abs and more potent neutralizing Abs than RBD alone or S2P protein against pseudotyped SARS-CoV-2 infection; elicited neutralizing Abs against pseudotyped SARS-CoV-2 B.1.1.7, B.1.351, and B.1.617 variants Elicited SARS-CoV-2 S-specific T-cell immunity (S2GΔHR2), and high GC B cell responses Protected NHPs from SARS-CoV-2 infection, with reduced virus replication and pathological damage 35, 39 and 71
S1-VLP S1 Mice Induced SARS-CoV-2 S/RBDspecific Abs and neutralizing Abs against SARS-CoV-2 WT and B.1.1.7 variant N/A N/A 76
SpFN S Hamsters Induced SARS-CoV-2 S/RBDspecific Abs and neutralizing Abs against pseudotyped SARS-CoV-2 WA1, B.1.1.7, and B.1.351 variants N/A Protected hamsters from SARS-CoV-2 (B.1.1.7 or B.1.351 variant) infection, with reduced virus replication and decreased weight loss, virus titers, and lung pathology 45
S-LuS S Mice Induced higher SARS-CoV-2 S-specific Abs and pseudovirus neutralizing Abs than those by S2P protein N/A N/A 77
S-Fer SΔC-Fer S S Mice Induced higher SARS-CoV-2 S/ RBD-specific Abs and pseudovirus neutralizing Abs than RBD monomer or S trimer protein N/A N/A 36
NVX-CoV2373 S Humans Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against infection of live SARS-CoV-2 Elicited SARS-CoV-2 S-specific CD4+ T-cell responses Protected vaccinated people against SARS-CoV-2 infection, showing efficacy against B.1.1.7 and B.1.351 variants; no serious adverse effects were identified, except for mild fever 38, 7880
Lipid nanoparticle-based SARS-CoV-2 mRNA vaccines
RBD-hFc RBD Mice Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against pseudotyped SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific Th1 cell responses Protected 70% of vaccinated hACE2-Tg mice from SARS-CoV-2 infection 85 and 86
mRNA-RBD RBD Mice Induced SARS-CoV-2 RBD- specific IgG Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 RBD-specific T-cell responses Protected hACE2-Tg mice from SARS-CoV-2 infection 83
RBD-LNP RBD Mice Induced SARS-CoV-2 and S1-LNP S1 SARS-CoV-1 RBD-specific IgG Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 RBD-specific T-cell, Tfh, GC B, and plasma cell responses N/A 47
RBD Full-length Δfurin RBD S Mice Induced SARS-CoV-2 S/RBDspecific IgG Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 RBD-specific Tfh, GC B, T-cell, B-cell, LLPC and MBC responses N/A 81 and 82
saRNA S Mice Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific T-cell responses N/A 89
LION/ repRNA-CoV2S S Mice NHPs Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against pseudotyped and/or live SARS-CoV-2 infection Elicited SARS-CoV-2 S1/RBD-specific T-cell responses (in spleen, lung (for mice) and PBMCs (for NHPs) N/A 53
CV07050101 S NHPs Induced SARS-CoV-2 S-specific IgG Abs without neutralizing activity Elicited SARS-CoV-2 S-specific T-cell responses N/A 87
LUNAR-COV19 S Mice Induced SARS-CoV-2 S-specific IgG and IgM Abs, S1/RBDspecific IgG Abs, and neutralizing Abs against live SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific CD8+ T and CD4+ T/Th1-dominant T-cell responses Protected hACE2-Tg mice from SARS-CoV-2 infection 90
mRNA-LNP S NHPs Induced SARS-CoV-2 S1/S2/ RBD-specific Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific memory B-cell, GC B cell, Tfh, and T-cell responses Protected infant NHPs from SARS-CoV-2 infection 94
MRT5500 S Mice Hamsters NHPs Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against pseudotyped or live SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific T-cell responses in mice and NHPs Protected hamsters from SARS-CoV-2 infection without weight loss and lung pathology 92
mRNA-1273 S Mice NHPs Humans Induced SARS-CoV-2 S-specific IgG Abs and neutralizing Abs against pseudotyped (wild-type and D614 mutant) and live SARS-CoV-2 infection Elicited SARS-CoV-2 S-specific CD4+ or CD8+ T-cell responses Protected immunized mice and NHPs from SARS-CoV-2 infection without causing disease enhancement effect; had protective efficacy in preventing COVID-19 disease in human; elicited local and systemic adverse effects (e.g., fatigue, chills, headache, myalgia, pain), allergic reactions, etc. 54, 88, 91, 97100 and 138
BNT162b1 BNT162b2 RBD S Mice NHPs Humans Induced dose-dependent, and SARS-CoV-2 RBD/S-specific Abs and neutralizing Abs against pseudotyped and live SARS-CoV-2 infection Elicited SARS-CoV-2 RBD-specific CD4+ and CD8+ T-cell responses Protected immunized mice and NHPs from SARS-CoV-2 infection; had protective efficacy in preventing COVID-19 disease in humans, with local and systemic reactions (fatigue, headache, myalgia, local pain, etc.), allergic reactions, and rare severe adverse events (for BNT162b2) 55, 84, 93, 101103, 131 and 140
Lipid nanoparticles displaying SARS-CoV-2 therapeutic agents
hsACE2 hACE2 Mice Secreted hACE2 in blood circulation and expressed hACE2 in bronchoalveolar lavage fluid; hACE2 bound SARS-CoV-2 RBD and neutralized pseudotyped SARS-CoV-2 infection N/A N/A 96

Abs, antibodies; ACE2, angiotensin-converting enzyme 2; BAL, bronchoalveolar-lavage; COVID-19, Coronavirus disease 2019; GC B, germinal center B; hACE2-Tg, human ACE2-transgenic; HR2, heptad repeat region 2; LLPCs, long-lived plasma cells; LuS, lumazine synthase; MBCs, memory B cells; NHPs, non-human primates; RBD, receptor-binding domain; S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; S2P, S protein with two proline mutations in the S2 subunit; Tfh, T follicular helper cells; WT, wild-type.