Vaccine and therapeutic development targeting hantavirus infections is a multifaceted and strives to be challenging undertaking. Our company is at the forefront of this critical work, leveraging scientific expertise and innovative approaches to accelerate vaccine and therapeutic development for pharmaceutical companies around the world.
Overview of Hantavirus Infection
Hanta virus infection is an infection that is caused by viruses in the Hantaviridae family. Such viruses can be contracted through contact with rodent's urine, saliva or excreta. Hantavirus infection has two main clinical conditions: Hantavirus Cardiopulmonary Syndrome (HCPS) and Haemorrhagic Fever with Renal Syndrome (HFRS). HCPS is limited to the countries in the Americas and has been observed to have a mortality rate of between 20%- 40% which is astoundingly high. HFRS, on the other hand, is present in the Eurasia region and has the case fatality rates between 0.1% - 15%. Which means it is least fatal compared to HCPS. Both present with a wide range of symptoms including myalgia, fever, pulmonary edema and even renal failure depending on the severity of the condition.
Fig.1 Cellular responses associated with hantavirus diseases. (Saavedra F., et al., 2021)
Vaccine Development for Hantavirus Infection
The development of the Hantavirus vaccine has gone through a sequence beginning with the use of Hantavax which are inactivated vaccines and work by stimulating immunity through the use of a virus, this in turn reduces HFRS incidence. Followed by that, recombinant protein vaccines make use of particular antigens such as the NP which induces great immune responses to any strain of the hantavirus. VLP vaccines were able to mimic the structure of the virus without incorporating the virus itself allowing for life long immunity. Currently in clinical trials are the DNA vaccines that encode protein molecules of the virus showcasing the ability and reigning potential to be effective triggers for the production of the particular viru.
Table 1 Hantavirus vaccine candidates. (Saavedra F., et al., 2021)
| Vaccine type |
Vaccine/antigens |
Animal model |
Immunogenicity evaluation |
| Recombinant proteins |
Nucleoprotein from ANDV, TOPV, DOBV, or PUUV |
Bank voles |
Specific CD8+ T-cell production
Cross-reactive response against PUUV |
| Yeast-expressed DOBV nucleoprotein |
Mice |
NP-specific IgG response, with IgG1, IgG2a, IgG2b and IgG3 subclass production
Th1/Th2 response
Cross-reactivity with HTNV and PUUV |
| Truncated recombinant PUUV nucleoprotein linked to bacterial membrane protein |
Mice |
NP IgG response
CD8+ T-cell response |
| DNA vaccines |
HTNV and ANDV M gene segments |
Rhesus macaques |
Neutralizing antibodies |
| HTNV M segment |
Rhesus macaques |
Neutralizing antibodies
Cross-reactivity with SEOV and DOBV |
| SNV M gene segment |
Syrian hamsters |
Neutralizing antibodies |
| HTNV/PUUV/SNV/ANDV M gene segment mix |
Rabbits |
Neutralizing antibodies |
| PUUV M gene segment |
Syrian hamsters |
Neutralizing antibodies
Protection against lethal ANDV infection, without nAbs |
| Virus-vectored |
Replication-competent VSV-vectored ANDV glycoproteins |
Syrian hamsters |
Neutralizing antibodies |
| Replication-competent VSV-vectored ANDV or SNV glycoproteins |
Syrian hamsters |
Cross-reactive IgG response
Neutralizing antibodies |
| Non-replicating Ad vector expressing N, Gn, Gc, or Gn/Gc |
Syrian hamsters (protection studies)
Mice (cytotoxicity assays) |
Neutralizing antibodies in SHs after challenge
Specific T CD8+ cell response |
| Virus-like particles (VLPs) |
HTNV-VLP with CD40L or GM-CSF incorporation |
Mice |
Neutralizing antibodies
Antigen-specific IFN-γ production
CTL response |
| Inactivated virus |
Hantavax (formalin-inactivated HNTV) |
Humans |
Neutralizing antibodies
B-cell response
Th1 response
Cytotoxic response |
Therapeutics Development for Hantavirus Infection
Ribavirin
One of the drugs that have been researched for treatment of hantavirus infection is ribavirn which is a broad spectrum antiviral. There is evidence to support that its effectiveness both in vitro and in vivo though clinical trials have not been uniformly consistent with some studies showing benefits for HFRS and others showing no or limited effect on HCPS.
Favipiravir
Favipiravir (T-705), an established agent of RNA-dependent RNA polymerase, has been primed to be an anti-hantavirus as well. It has demonstrated some efficacy in vitro against Sin Nombre Virus (SNV) and Andes Virus (ANDV) and seems to be safe for use in human trials.
Lactoferrin
Lactoferrin is an iron-storing glycoprotein which has been investigated for its ability to inhibit Hantaviruses. The studies that were conducted, both in vitro and in vivo, have illustrated lactoferrin in adverting cells from adsorbing viruses, thus proving its potential use as a drug.
Vandetanib
Vandetanib, an inhibitor of tyrosine kinase, has recently been evaluated for its ability to reduce increased vascular permeability due to severe Hantavirus infections. It has, however, been effective is preclinical studies whilst aiming for VEGF-receptor 2 blocking which vandetanib works.
Our Services
Offering a unique solution to the niche requirement, we focus on constructing vaccines and devising therapies fitting for hantavirus infections. Our multidisciplinary team includes experts from the fields of virology, immunology and pharmacology working together to transform this crucial sphere through cutting-edge innovations.
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
Disease Models
- Immunocompetent Syrian Hamsters Infected with SNV
- Syrian Hamsters Infected with ANDV
- Immunocompetent Deer Mice Infected with SNV
- Other Hantaviruse Infections: Hantaan (HTNV), Puumala (PUUV), Dobrava (DOBV), and Seoul (SEOV)
Our preclinical research services are strategically crafted to accelerate the progress of potent vaccines and therapies for hantavirus infections. Employing cutting-edge technologies and methodologies, we conduct thorough evaluations of the immunogenicity, safety, and efficacy of the candidates in our pipeline. If you are interested in our services, please feel free to contact us.
References
- Saavedra, Farides, et al. "Immune response during hantavirus diseases: implications for immunotherapies and vaccine design." Immunology 163.3 (2021): 262-277.
- Dheerasekara, Kalpa, Saranga Sumathipala, and Rohitha Muthugala. "Hantavirus infections-treatment and prevention." Current treatment options in infectious diseases 12 (2020): 410-421.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
