Table 3.
Chronological overview of henipavirus vaccines in development, by platform
| Vaccine regimen and administration route | Animal models used | Henipavirus challenge strain | Reference | |
|---|---|---|---|---|
| Viral vectors | ||||
| Recombinant vaccinia viruses (modified vaccinia virus Ankara) expressing NiV-M or HeV F, G, or N | Single dose (intraperitoneal) | Mice | None | 56 |
| Vaccinia virus vector (NYVAC) expressing NiV-M G or F | 2 doses, 1 month apart (subcutaneous) | Syrian golden hamsters | NiV-M | 57 |
| Canarypox vector (ALVAC) expressing NiV-M G or F | 2 doses, 14 days apart (intramuscular) | Pigs* | NiV-M | 58, 59 |
| Venezuelan equine encephalitis virus expressing HeV or NiV-M G or F | 3 doses on weeks 0, 5, and 18 (footpad inoculation) | Mice | None | 60 |
| Replication-defective VSV-DG vector expressing NiV-M G or F | Single dose (intranasal or intramuscular) | Mice | None | 61 |
| Newcastle disease virus vector expressing NiV-M F or G | 2 doses, 4 weeks apart (intramuscular) | Mice, pigs* | None | 62 |
| Single-cycle replication VSV-DG vector expressing NiV-B G and/or F | Single dose (intramuscular) | Ferrets | NiV-M | 63† |
| Adeno-associated virus vector expressing NiV-M G | Single dose (intramuscular) | Syrian golden hamsters | NiV-M and HeV | 64 |
| Measles virus vaccine vectors (HL and Ed strains) expressing NiV-M G | 2 doses, 21 or 28 days apart (intraperitoneal [Syrian golden hamsters] or subcutaneous [African green monkeys]) | Syrian golden hamsters, African green monkeys | NiV-M | 65 |
| Live-attenuated rVSV-ZEBOV-GP vector expressing NiV-M G, F, or N | Single dose (intraperitoneal) | Syrian golden hamsters | NiV-M | 66‡ |
| Single-cycle replication VSV-DG vector expressing NiV-M G or F | Single dose (intramuscular) | Syrian golden hamsters | NiV-M | 67 |
| Live-attenuated and beta-propiolactone-inactivated VSV or rabies virus vaccine vectors expressing codon-optimised HeV G | Single dose (live) or three doses (beta-propiolactone), on weeks 0, 2, and 3 (intramuscular) | Mice* | None | 68 |
| Live-attenuated rVSV-ZEBOV-GP vector expressing NiV-M G | Single dose (intramuscular) | African green monkeys | NiV-M | 69‡ |
| Live-attenuated rVSV-ZEBOV-GP vector expressing NiV-M G | Single dose (intraperitoneal) | Syrian golden hamsters | NiV-M | 70‡ |
| Canarypox vector (ALVAC) expressing HeV G or F | 2 doses, 21 days apart (intramuscular) | Syrian golden hamsters and ponies (horses) | None | 71 |
| Non-replicating VSV-DG vectors expressing NiV-M G and/or F | Single dose (intranasal or intracranial) | Mice | None | 72 |
| Live-attenuated and beta-propiolactone-inactivated rabies virus vaccine vector expressing NiV-B G | Single dose (live) or 2 doses (beta-propiolactone), 28 days apart (intramuscular) | Mice | None | 73 |
| Single-cycle replication VSV-DG vector expressing NiV-B G and/or F | Single dose (intramuscular) | African green monkeys | NiV-B | 74† |
| Chimpanzee adenovirus vector expressing NiV-B G | Single or two doses, 28 days apart (intramuscular) | Syrian golden hamsters | NiV-M, NiV-B, and HeV | 75 |
| Modified vaccinia virus Ankara expressing NiV-M sG or G | Single or 2 doses, 21 days apart (intraperitoneal or intramuscular) | IFNAR −/− mice | None | 76 |
| Recombinant rabies viruses Evelyn-Rokitnicki-Abelseth strain, rERAG333Eexpressing NiV-M G or F | 2 doses, 8 weeks apart (oral) | Mice and pigs* | None | 77 |
| Bovine herpes virus 4 or canarypox vectors (ALVAC) expressing NiV-M G or F | 2 doses, 3 weeks apart (intramuscular) | Pigs* | None | 5, 78 |
| Protein subunits§ | ||||
| sGNiV-M or sGHeV in CSIRO triple adjuvant (Montanide/QuilA/DEAE-dextran) | 3 doses, 2 weeks apart (subcutaneous) | Cats | NiV-M | 79 |
| Recombinant soluble HeV G glycoprotein in CpG plus Alhydrogel adjuvant | 2 doses, 21 days apart (intramuscular) | Cats | NiV-M | 80 |
| Soluble trimeric forms of HeV and NiV-M F proteins (sFGCNt) in Sigma Adjuvant System adjuvant | 4 doses, each 30 days apart (intraperitoneal or subcutaneous) | Mice | None | 81 |
| Recombinant soluble HeV G glycoprotein in CpG and Alhydrogel adjuvant | 2 doses, 21 days apart (intramuscular) | African green monkeys | NiV M | 82 |
| Recombinant soluble HeV G glycoprotein in Alhydrogel and CpG adjuvant | 2 doses, 20 days apart (subcutaneous) | Ferrets | NiV B | 83 |
| Recombinant soluble HeV G glycoprotein in Alhydrogel with or without CpG adjuvant | 2 doses, 21 days apart (intramuscular) | African green monkeys | HeV | 84 |
| Recombinant soluble HeV G glycoprotein (produced in 293 or Chinese hamster ovary cells) in a proprietary adjuvant (Zoetis, Inc) | 2–5 doses, weeks 0 and 3, then at 6 months and then yearly (intramuscular) | Horses* | HeV | 85, 86 |
| Recombinant soluble HeV G glycoprotein in a proprietary adjuvant (Zoetis, Inc) | 2 doses, 21 days apart (intramuscular) | Pigs* | NiV-M and HeV | 87 |
| Recombinant soluble HeV G glycoprotein in alhydrogel + CpG adjuvant | 2 doses, 20 days apart (subcutaneous) | Ferrets | HeV | 88 |
| Molecular clamp-stabilised F protein (mcsF) | 2 doses, 3 weeks apart (intramuscular) | Pigs* | NiV-M | 5 |
| Multiple pre-fusion-stabilised F and oligomeric G proteins derived from NiV-M and formulated in aluminum hydroxide | 2 doses, 3 weeks apart (intramuscular) | Mice | None | 89 |
| Monovalent, bivalent, and tetravalent Fc-linked G proteins from NiV-M, HeV, GhV, and MojV formulated in CpG and Alhydrogel | 2 doses, 3 weeks apart (intramuscular) | Mice | None | 90 |
| Recombinant soluble HeV G glycoprotein, produced in HEK-293 cells, formulated in Alhydrogel | Single dose or 2 doses, 4 weeks apart (intramuscular) | African green monkeys | HeV (Brisbane) and NiV B | 91 |
| Virus-like particles | ||||
| Virus-like particles containing NiV-M M, G, and F¶ | 3 doses on days 0, 15, and 29 (subcutaneous) | Mice | None | 92 |
| Virus-like particles containing NiV-M M, F, and G, formulated in various adjuvants (alum, monophosphoryl lipid A, and CpG)¶ | Single dose or 3 doses on days 0, 21, and 42 (intramuscular) | Syrian golden hamsters | NiV-M | 93 |
| Virus-like particles containing NiV-M M and F or G in Sigma Adjuvant System | 3 doses on weeks 0, 3, and 5 (intramuscular) | Rabbits | None | 94 |
| Virus-like particles containing NiV-M F and G and HeV M | 3 doses on weeks 0, 3, and 6 (intraperitoneal) | Mice | None | 95 |
| Cellular debris | ||||
| Pellets and supernatants from sF9 cells expressing recombinant NiV-M F and G proteins in a baculovirus system | 2 doses, 3 weeks apart (intramuscular and intraperitoneal) | Mice | None | 96 |
| DNA | ||||
| Plasmids encoding codon-optimised NiV-M F and/or G | 2 doses, 4 weeks apart (intramuscular) | Mice | None | 97 |
| Plasmids encoding NiV-M F and/or G | Single dose (intramuscular) followed by electroporation | Mice | NiV-M pseudovirus | 98 |
| mRNA | ||||
| HeV G codon-optimised mRNA in liquid nanoparticles | Single dose (intramuscular) | Syrian golden hamsters | NiV-M | 99 |
| mRNA-1215, mRNA encoding NiV-M F and G in liquid nanoparticles | To be determined | Undisclosed preclinical development | To be determined | 100 |
GhV=Ghanaian bat henipavirus. GP=glycoprotein. HeV=Hendra virus. MojV=Mojiang henipavirus. NiV=Nipah virus. NiV-B=Nipah virus Bangladesh. NiV-M=Nipah virus Malaysia. rVSV=recombinant vesicular stomatitis virus. VSV=vesicular stomatitis virus. ZEBOV=Zaire Ebola virus.
*
These vaccines are intended primarily for veterinary use.
†
The single-cycle replication VSV-DG vector expressing NiV-B G and/or F is identical in these studies.
‡
The live-attenuated rVSV-ZEBOV-GP vector expressing NiV-M G is identical in these studies.
§
The soluble HeV G protein is identical in all studies using different adjuvant formulations.
¶
The virus-like particles are identical in these studies using different formulations.