Table 3.
Ongoing and completed clinical trials concerning nasal vaccines.
| Ongoing clinical trials | ||
|---|---|---|
| Disease/Clinical trial number | Study characteristics | Stage |
| Anthrax/NCT04148118 [111] | Evaluation of the safety and immunogenicity of intranasally administrated BW-1010 vaccine to healthy adults. The vaccine comprises of adjuvanted rPA in nanoemulsion formulation. It will be administered through nasal sprayers and nasal drops. Nasal samples and serum will be assessed for total IgA, anti-rPA IgA and IgG and toxin neutralization antibodies | Phase 1 |
| Influenza type A, Respiratory syncytial virus (RSV) infections/NCT02755948 [128] | Vaccination of healthy adult volunteers with Influenza and RSV antigens through nasal drops. Cell mediated immunity against these viruses will be examined | Recruiting |
| Meningitis/NCT04135053 [18] | Nasal inoculation of healthy adults with reconstituted and lyophilized Neisseria lactamica. The study aims to examine safety and immunogenicity, and determine the required dose for the induction of colonization in 80 % of the volunteers | Recruiting |
| Meningitis/NCT04665791 [129] | Dose-ranging nasal inoculation of healthy Malian adults with reconstituted and lyophilized Neisseria lactamica. The optimal dose and the immunization ability will be examined | Recruiting |
| RSV infections/NCT01893554 [130] | Evaluation of safety and immune responses against RSV infections. Healthy RSV-seropositive and RSV-seronegative infants and children will be vaccinated with nasal drops | Phase 1 |
| Completed clinical trials | ||
| Indication/Registration number | Study main characteristics | Stage |
| Chronic Hepatitis B/NCT01374308 [19], [20] | Comparison between therapeutic vaccination with HBsAg and HBcAg (NASVAC) and the pegylated interferon alfa 2b (Peg-IFN). Higher reduction of HBV DNA levels in serum and increase of alanine aminotransferases levels compared to Peg-IFN recipients. | Phase 3 |
| Diphtheria/[119] | Immunization with the genetically inactivated mutant diphtheria toxoid CRM197 in a polycationic polysaccharide chitosan nanoformulation. Antitoxin neutralizing activity was observed, equivalent to intramuscular vaccination. The presence of chitosan enhanced the immunogenicity. SIgA induction was not as high as expected with the first inoculation. | Phase 1 |
| HIV-1 infection/NCT00122564 [120] | Transmucosal (nasal or vaginal) administration of HIV-1 vaccine with the recombinant gp-160, with or without the adjuvant DC-chol (cationic lipid). | Phase 1 |
| HIV-1 infection/NCT01084343 [104] | In administration of HIV-1 vaccine (MYM-V101) after two intramuscular doses to female volunteers. MYM-V101 is a virosomal vaccine that carries on its surface the lipid peptide P1, derived from the gp41 of HIV-1. Evaluation of the adverse events and immune responses. Induction of the vaginal and rectal P1-specific IgGs, vaginal P1-IgAs and, specific IgG and IgA antibodies in serum | Phase 1 |
| HIV infection/NCT01473810 [105] | IN administration of Vacc-4x cause dose-dependent immunogenicity. Induction of T-cell (CD8+, CD4+) and mucosal and systemic humoral responses. | Phase 1,2 |
| HIV/NCT00369031 [131] | Estimation of safety and immunogenicity of nasal vaccine, containing HIV-glycoprotein 140 mixed with a toxoid or a liquid adjuvant (Labile Toxin mutant: LTK63) | Phase 1 |
| Influenza type A, B/NCT03023553 [132] | Comparison of the immunogenicity against seasonal influenza, between intramuscular administration of trivalent inactivated Fluzone® vaccine and IN delivery of live attenuated FluMist® vaccine. | Phase 4 |
| Influenza type A, B/[133] | Administration of inactivated, trivalent influenza virus vaccine using chitosan as delivery system. | Phase 1 |
| Influenza type A (GamFluVac)/[134] | Comparative assessment of immunity responses derived from two different methods of IN administration of GamFluVac (nasal drops and nasal spray) | Phase 2 |
| Influenza type A (H1N1, H3N2) and B/[135] | Virosomal vaccine adjuvanted with Escherichia coli HLT elicits humoral and cell-mediated responses and high titers of IgA neutralizing antibodies at the mucosa, comparable to parenteral vaccination | Phase 2 |
| Influenza type A (H1N1, H3N2) and B (Fluzone)/[136] | IN administration of the quadrivalent influenza vaccine Fluzone® and comparison of the immunogenicity after intramuscular and IN vaccination | Phase 1 |
| Influenza type A (H1N1, H3N2) and B/[137] | Virosomal vaccines administered through intranasal sprays, Escherichia coli heat-labile toxin (HLT) adjuvanted vaccines provoked comparable humoral immune responses with parenteral vaccination, higher IgA titers in the saliva after two nasal doses | Phase 1 |
| Influenza type A (H1N1, H3N2) and B/[57], [58] | Trivalent subunit influenza vaccine using Proteosome™ as delivery system elicits serum and mucosal immune responses, without severe adverse reactions. | Phase 1,2 |
| Influenza type A (H1N1)/[56] | Evaluation of the monovalent influenza vaccine connected with outer membrane proteins (OMP) extracted from N. meningitidis, employing Proteosome™ as delivery system. Well-tolerated vaccine, causing serum HAI antibodies and HA-specific sIgA. | Phase 1 |
| Influenza type A (H5N1)/NCT01258062 [138] | GelVac™ nasal powder H5N1 influenza vaccine, evaluation of frequency and severity of the adverse effects | Phase 1 |
| Μeningitis, Diphtheria/[17] | Comparison of immunogenicity between intramuscular injection and nasal insufflations of Neisseria meningitidis serogroup C polysaccharide (MCP) with diphtheria toxoid (CRM197) conjugated vaccine. Induction of MCP-specific and CRM197-specific IgG, MCP-specific sIgA, serum bactericidal antibodies and diphtheria toxin-neutralizing activity. | Phase 1 |
| Norovirus infections/NCT00806962 [71], [112] |
Norwalk VLP vaccine with GI.1 genotype adjuvanted with MPL and chitosan. Two studies examining the effect of different antigen dosages. No serious vaccine-related adverse events were reported. High immunogenicity with Norwalk VLP-specific IgG and IgA titers related to the dose. | Phase 1 |
| Pertussis/NCT01188512 [98], [99] | IN delivery of BPZE1, a live attenuated nasal pertussis vaccine with a genetically modified Bordetella pertussis strain. Induction of immune responses to all adult volunteers can lead to the use of this vaccine as THE first vaccination of young infants, before the injectable one. | Phase 1 |
| Pertussis/NCT02453048 [100], [101] | Single IN administration of BPZE1. Induction of B. pertussis–specific antibody responses, Th1-type cellular responses, and killing mechanisms. | Phase 1 (Ib) |
| Pertussis/NCT03541499 [102] | Single IN administration of BPZE1. Evaluation of the optimal dose, humoral and mucosal immunogenicity. | Phase 2 |
| Pertussis/NCT04036526 [139] | Comparison of doses and application methods of GamLPV, a live IN Bordetella pertussis vaccine | Phase 1,2 |
| Respiratory illness from human Parainfluenza virus type 2 (HPIV2)/NCT01139437 [121] | Safety of and immune response of live attenuated intranasally administered HPIV2 vaccine. This approach activates antibody-mediated, the cell-mediated and mucosal immune responses. | Phase 1 |
| Shigellosis/[59] | Shigella flexneri 2a vaccine connected to meningococcal outer membrane proteins of Proteosomes. Dose-escalated clinical trial. Dose-related immune reactions, containing S. flexneri 2a lipopolysaccharide-specific IgA, IgG and IgM antibody-secreting cells. | Phase 1 |
| Shigellosis/NCT00485134 [115], [114] | IN administration of Shigella flexneri 2a Invaplex 50 vaccine (subunit vaccine), via the Dolphin™ spray device lead to more effective immune responses than the droplet method, by the induction of the antibody secreting cells (ASC) and the antigen-specific mucosal and intestinal IgA | Phase 1,2 |
| Tuberculosis/[108] | Subunit tuberculosis vaccine with a toxoid adjuvant. Αssessment of safety and immunogenicity. | Phase 1 |
| Tuberculosis/NCT03017378 [109] | IN and sublingual tuberculosis vaccine delivery (TB/FLU-01L) to healthy adults, already vaccinated with the common tuberculosis vaccine (BCG) | Phase 1 |