The development of vaccines and therapies for hantavirus infections is a complex and multifaceted endeavor. 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
Hantavirus infections are caused by a group of viruses belonging to the Hantaviridae family, which are typically transmitted to humans via contact with rodent excreta, urine, or saliva. The two primary clinical manifestations of Hantavirus infection are Hantavirus Cardiopulmonary Syndrome (HCPS) and Haemorrhagic Fever with Renal Syndrome (HFRS). HCPS is predominantly found in the Americas and is associated with high mortality rates, ranging from 20% to 40%. In contrast, HFRS is more common in Eurasia, with case fatality rates varying from 0.1% to 15%. Both diseases exhibit a range of symptoms, including fever, myalgia, and in severe cases, pulmonary edema and renal failure.
Fig.1 Cellular responses associated with hantavirus diseases. (Saavedra F., et al., 2021)
Vaccine Development for Hantavirus Infection
Hantavirus vaccine development has progressed through various generations, starting with inactivated vaccines like Hantavax, which reduce HFRS incidence by utilizing inactivated viruses to stimulate immunity. Next, recombinant protein vaccines leverage specific antigens, such as the NP, to elicit robust immune responses across different hantavirus strains. VLP vaccines have been designed to replicate the virus's structure without the live virus, thus promoting long-term immunity. Lastly, DNA vaccines, which introduce genetic material encoding viral proteins, are in clinical trials, demonstrating the potential for effective hantavirus protection.
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
As a broad-spectrum antiviral, ribavirin has been tested for the therapeutic of hantavirus infections. Although it has shown some efficacy in vitro and in vivo, clinical trial results have been mixed, with some studies demonstrating benefits in HFRS cases, while others show no significant effect in HCPS cases.
Favipiravir
Favipiravir (T-705), a potent inhibitor of RNA-dependent RNA polymerase, has emerged as a promising antiviral against Hantaviruses. In vitro studies have shown it to be effective against Sin Nombre Virus (SNV) and Andes Virus (ANDV), with a favorable safety profile in human clinical trials.
Lactoferrin
Lactoferrin, an iron-binding glycoprotein, has been studied for its antiviral activity against Hantaviruses. Both in vitro and in vivo studies have shown lactoferrin to inhibit virus adsorption to cells, thus demonstrating its potential as a therapeutic agent.
Vandetanib
Vandetanib, a tyrosine kinase inhibitor, has been studied for its potential in managing the increased vascular permeability associated with severe Hantavirus infections. By targeting VEGF-receptor 2 activation, vandetanib has shown promise in preclinical studies.
Our Services
Specializing in the development of vaccines and therapies for hantavirus infections, our array of services is designed to cater to this specific area of need. Our team of experts spans various disciplines, including virology, immunology, and pharmacology, working collaboratively to push the boundaries of innovation in this critical field.
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.
