The Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus that is responsible for a multitude of diseases, the most notable being adult T-cell leukemia or lymphoma (ATLL) alongside HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP). Our company provides an extensive range of services tailored for the development of HTLV-1 vaccines and therapies.
Overview of HTLV-1
Human T-lymphotropic virus type 1 (HTLV-I) is a virus belonging to the Deltaretrovirus class. This type of retrovirus is passed on through sexual intercourse, contaminated blood transfusions and breastfeeding. HTLV–I is associated with several disorders including adult T-cell leukemia-lymphoma (ATLL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). In the world, HTLV-1 is prevalent in about 15-20 million people, the vast majority of whom are asymptomatic. At the same time, diseases develop in 2-6% of the carriers, which indicates the requirement to develop efficient therapies and effective vaccination strategies.
Fig.1 Expansion of human T-lymphotropic virus 1 infection (HTLV-1). (Soltani A., et al., 2019)
Vaccine Development for HTLV-1
- DNA-based Vaccines
The introduction of plasmids coding for HTLV-1 antigens including Tax and envelope proteins into host cells for the induction of an immune response is called DNA vaccination. In the preclinical models, these plasmid vectors were effective as a few studies demonstrated the generation of specific CTLs and neutralising antibodies.
- Viral Vector-based Vaccines
Another method is the use of HTLV-1 viral vectors like adenovirus or vaccinia virus. These types of vectors can effectively deliver relevant antigens to the immune system, stimulating strong cellular and humoral responses. One of those examples would be recombinant vaccinia virus that expresses HTLV-1 envelope proteins which in turn has been shown to provide strong long term immunity in animals.
- Peptide/Protein-based Vaccines
Peptide vaccines target the immunodominant regions of HTLV-1 proteins and aim at evoking a strong protein specific CTL response for example targeting regions like Tax protein. An example of this includes multi-epitope vaccines which aim to target and provoke a response for HTLV-1 antigens. The response produced is greater in scope than if it were aimed at just a single epitope.
Table 1 Characteristics of peptide and protein vaccine studies. (Seighali N., et al., 2023)
| Type of Study |
Host |
Vaccine immunogen content |
Author |
Year |
Country |
| in vivo |
BALB/c (Charles River), C57BL/6 (CharlesRiver) and CFW/D |
Inclusion bodies of the envelope protein (env-I.B.) with or without the addition of an adjuvant |
Arp, J |
1993 |
USA |
| in vivo |
Female New Zealand White rabbits and inbred female WWQdj, Fisher 433 (F433)/Qdj rats, Inbred female BN/Sea, LewisiSea rats, d ACI/Jcl rats |
2 vaccines: T and B cell epitope-based peptide vaccine constructed from the conjugation of gp46 (aa 181–210) and (181–203) with a branched polylysine oligomer |
Baba, E |
1995 |
Japan |
|
|
| in vivo |
Female inbred strains of mice (BALB/c, C3H/ HeJ, and C57BL/6) were obtained from Jackson Laboratories (Bar Harbor, Maine), and outbred ICR mice were obtained from Harlan Industries (Indianapolis, Ind.). Rabbits |
Synthetic chimeric and b-template peptide structures were created, integrating established human T-lymphotropic virus type 1 (HTLV-1) B- and T-cell epitopes derived from the surface envelope protein gp46, specifically SP2 [aa 86 to 107] and SP4a [aa 190 to 209], alongside versatile T-cell peptides |
Lairmore |
1995 |
USA |
| in vitro and in vivo |
Eight- to ten-week-old transgenic HLA-B-3501 transgenic mice of both sexes |
Synthetic HTLV-1 peptides combined with the lipohexapeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-lysyl-lysyl-lysine, a biocompatible adjuvant that functions independently of Thepitope |
Schönbach |
1996 |
Japan |
| in vivo |
Four-week-old female F344/N Jcl-rnu/rnu (nu/nu or athymic) rats and F344/N Jcl-rnu/ + (nu/ +) rats |
Synthetic oligopeptides corresponding to the Tax-epitope(180–188) |
Hanabuchi, S |
2001 |
Japan |
| in silico |
NA |
9 Cytotoxic T Lymphocytes, 6 Helper T Lymphocytes, and 5 Linear B Lymphocytes epitopes, joint through linkers and adjuvant |
Tariq |
2021 |
Pakistan |
| in vivo and in vitro |
male 6 to 8 weeks pathogen-free BALB/c mice |
Fc-fusion multi-immunodominant recombinant protein (Tax-Env: mFcγ2a and Tax-Env: His) |
shafifar |
2022 |
Iran |
Therapeutics Development for HTLV-1
Reverse Transcriptase Inhibitors
Considering the fundamental function that reverse transcriptase performs in the viral life cycle, HTLV-1 therapeutics targeting this enzyme have been developed. NRTIs like zidovudine and tenofovir have been found useful in lowering the viral load both in vitro and during clinical use.
Immunomodulatory Therapies
Promising results have been observed during clinical trials that employed therapeutic strategies meant to enhance the immune response of the host, for instance, the use of interferons and monoclonal antibodies. These therapies are devised to augment the immune response of the host towards HTLV-1-infected cells.
Protease Inhibitors
HIV-1 protease inhibitors have demonstrated at least some degree of activity against HTLV-1, though classed in the least effective antivirals due to how different the protease structure of the two viruses is. These viral proteases are of pivotal importance as they also assist in restricting the creation of infectious particles.
Integrase Inhibitors
Raltegravir is an integrase inhibitor which conceivably prevents the incorporation of viral DNA into a transcript. These inhibitors have shown some efficacy in dampening viral replication and proviral loads within HTLV-1 infected cells.
Our Services
We have a dedicated team that works on developing sophisticated vaccine and therapy services for HTLV-1 infection which is something that we specialize in at our company. Looking for innovative solutions is what we pride ourselves in as our team utilizes new technologies to do therapeutic development.
Disease Models
- HTLV-1 Carrier Mice: Created by inoculating MT-2 cells (an HTLV-1 producing cell line) into mice such as C3H/HeJ and BALB/c.
- Tax Gene Modified Mice
- HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Models
Our company is committed to advancing preclinical research for HTLV-1 infection. Our preclinical research services are designed to accelerate the discovery and development of effective vaccines and therapies:
- Animal Models: We utilize well-characterized animal models of HTLV-1 infection to evaluate the safety and efficacy of novel therapeutic candidates.
- Immunogenicity Studies: Comprehensive immunogenicity assessments are conducted to evaluate the immune responses elicited by vaccine candidates, including T-cell and antibody responses.
- Safety Assessments: We conduct thorough safety evaluations to identify any potential adverse effects associated with vaccine candidates or therapeutic agents.
- Data Analysis and Reporting: Our team provides detailed data analysis and comprehensive reports to facilitate decision-making in the development pipeline.
If you are interested in our services, please feel free to contact us.
References
- Soltani Arash, et al. "Molecular targeting for treatment of human T-lymphotropic virus type 1 infection." Biomedicine & Pharmacotherapy 109 (2019): 770-778.
- Raza, Md Thosif, et al. "Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1)." PloS one 16.4 (2021): e0248001.
- Seighali, Niloofar, et al. "Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies." BMC Infectious Diseases 23.1 (2023): 320.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
