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. 2023 May 11;41(24):3589–3603. doi: 10.1016/j.vaccine.2023.05.011

Table 2.

Preclinical studies of nasal vaccines against influenza subtypes and other viruses.

Indication Influenza type/Antigen Adjuvant/Excipient Key outcome
Acquired Immune Deficiency Syndrome (AIDS) from HIV-1
HIV-1 DNA plasmids encoding gagp37 of subtype B [122] N3 (cationic lipid-based adjuvant) [81] ↑ of HIV-1-specific humoral immune response without causing damage to the nasal epithelium and interfering with the CNS
Recombinant multiepitopic protein from HIV-1 (CR3) [123] HBsAg (Hepatitis B virus surface antigen), HBcAg (Hepatitis B virus core antigen) High titers of Th1 cells in spleen and IFNγ secreting cells in the intestine, less anti-CR3 antibodies at the vagina, simultaneously immunity against HBV
Acute otitis media from non-typeable Haemophilus influenzae (NTHi)
Outer membrane protein (OMP) from NTHi (strain 76) [116] Monophosphoryl lipid A (MPL: TLR-4 agonist) MPL augmented OMP-specific IgA titers in the nasopharynx
Anthrax AdVAV (replication-deficient adenovirus type 5-vectored vaccine) encoding the protective antigen (PA83) from B. anthracis[124] Faster induction of immune response and higher levels of anti-PA IgG and toxin neutralized antibodies compared to intramuscular immunization against B. anthracis
Anti-protective antigen (PA) against Bacillus anthracis toxin alone or conjugated with a 10-mer peptide of capsule of B. anthracis[68] Monophosphoryl Lipid A (MPL) with or without Chitosan (ChiSys™) Protection against B. anthracis infection through high levels of anti-PA IgG in serum, when the vaccine combines PA protein with capsule epitopes and chitosan
Recombinant Bacillus anthracis protective
antigen (rPA) [110]
Aluminum hydroxide or unmethylated, phosphorothioate-linked, CpG-containing oligonucleotides Powder formulations achieved higher protection against anthrax challenge compared to liquid, unit-dose
disposable devices
rPA alone or conjugated with a 10-mer peptide of capsule of B. anthracis[66] MPL, ChiSys ® Dry powder anthrax vaccine induces immunization
Cutaneous leishmaniasis
Whole lyophilized strains from Leishmania amazonensis (LaAg) [118] ↑ of the Τh1, CD4 + and CD8 + T cells levels, ↓ of the Treg subpopulations, protection against cutaneous leishmaniasis and visceral leishmaniasis
Ebola virus disease
Ebola virus envelope glycoprotein (GP) [117] CTA1-DD (subunit of cholera toxin combined
with two Ig-binding domains of staphylococcal protein A)
The CTA1-DD adjuvant enhanced the humoral, cellular and mucosal immune response through IgG, Th1, IFN-c/IL-4 secreting cells and IgA in vaginal lavages
Hepatitis B
HBsAg, HBcAg [113] Influenza surface protein haemagglutinin (HA) from H1N1 HA complexed liposomes Influenza surface protein haemagglutinin
Influenza H7N9 avian influenza A virus/Recombinant H7 protein [80] PEG-b-PLACL (PELC: squalene-based oil-in-water emulsion) and CpG compared to poly(I:C) and flagellin (plasmid-encoded TLR5 agonist) ↑ of IgG and IgA titers in serum and spleen even in low doses
Influenza A virus (H1N1)/Whole inactivated virus [81] N3 (cationic lipid-based adjuvant), pFliC(-gly) (flagellin derived adjuvant) ↑ of humoral and cellular influenza specific immune response
Influenza A virus (H3N1, H3N2, H1N1)/Pam2Cys [125] Pegylated Pam2Cys (PEG-Pam2Cys: TLR2 agonist) Induction of pulmonary innate immune response and adaptive immunity
Influenza A virus (H5N1)/Recombinant HA protein [88] Thermal-sensitive hydrogel from HTCC (chitosan derivative) and α, β-GP (α, β-glycerophosphate) ↑ of the residence time in nasal cavity and extended transepithelial transport, antigen-specific systemic and mucosal immunity through cellular and humoral response
Swine influenza virus/Inactivated antigen (H1N2-OH10) [14] Chitosan, poly(I:C) ↑ of HI serum titers and antigen-specific IFN-γ response, memory cells, Th1, Th2 and γ, δ T-cells in pulmonary and distant lymphoid sites
Norovirus infections
Bivalent formulation with GI and GII.4 VLPs [72] GelSite ™ Systemic and mucosal immunogenicity occurs after two doses of the VLPs
Self-assembling Norwalk virus-like particles (NV VLPs) [73] GelSite ™ (inert in-situ gelling polysaccharide), gardiquimod (TLR7 agonist) GelSite-based dry powder formulations induced systemic and mucosal antibody titers equal to those achieved by liquid formulations
Pertussis
Acellular pertussis vaccine consisting of 2 or 3B. pertussis antigens (including recombinant pertussis toxin, TLR2 lipoprotein ligands from B. pertussis) [15], [16] c-di-GM (intracellular receptor stimulator of interferon genes agonist), LP1569 (TLR2 agonist from B. pertussis) Induction of Th1, Th17 and IgG2 antibody response, ↑of IL-17-secreting respiratory tissue memory cells
Respiratory syncytial virus (RSV) infections
Plasmid DNA encoding the CTL epitope from the M2 protein of RSV [78] Chitosan ↑ the induction of CTL response comparable to those induced via intradermal route
SARS-CoV-2
Chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike (S) protein modifying it with two proline substitutions in the S2 subunit [89] Protection of upper and lower respiratory tract from SARS-CoV-2 infection, ↑of the levels of serum and mucosal IgA after a single dose compared to intramuscular immunization
Lipid nanoparticle‑based
SARS‑CoV‑2 proteins and mRNA vaccines [96]
NP-monosodium urate adjuvant Induction of Th1 and Th2 immune responses and of antibodies secretion
Tetanus
Tetanus toxoid [67] Alginate microspheres, cross-linked dextran
microspheres, quillaja saponins
↑ of sIgA and serum IgG titers, ↑ of mucoadhesion
Tuberculosis BCG vaccine (different Mycobacterium bovis strains) [126], [127] ↑ of the CD8 T cells, interferons and interleukins levels in spleen compared to subcutaneous immunization, ↔ pulmonary protection
Messenger RNA of Hsp65 protein from Mycobacterium leprae[107] Production of IL-10 and TNF-α against Hsp65 in spleen, nitric oxide production from TLR7 cells