Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus associated with a spectrum of diseases, most notably adult T-cell leukemia/lymphoma (ATLL) and 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
T-lymphotropic virus type 1 (HTLV-1) is a retrovirus classified under the Deltaretrovirus genus. It is primarily transmitted through breastfeeding, sexual contact, and contaminated blood products. HTLV-1 is linked to various diseases, notably adult T-cell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Globally, around 15-20 million individuals are infected, with the majority remaining asymptomatic. However, symptomatic diseases develop in 2-6% of carriers, underscoring the pressing need for effective therapeutic interventions and vaccine 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
DNA vaccines involve the introduction of plasmids encoding HTLV-1 antigens, such as Tax and envelope proteins, into host cells to induce an immune response. These vaccines have shown promise in preclinical models, with some studies reporting the induction of specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies.
- Viral Vector-based Vaccines
Using viral vectors, such as adenovirus or vaccinia virus, to deliver HTLV-1 antigens is another strategy. These vectors can efficiently present antigens to the immune system, leading to robust cellular and humoral immune responses. Notable examples include the use of recombinant vaccinia virus expressing HTLV-1 envelope proteins, which have demonstrated the ability to induce long-term immunity in animal models.
- Peptide/Protein-based Vaccines
Peptide vaccines focus on specific immunodominant regions of HTLV-1 proteins. By targeting these regions, such as the Tax protein, these vaccines aim to elicit a strong and specific CTL response. Examples include multi-epitope vaccines designed to target multiple HTLV-1 antigens simultaneously, enhancing the breadth of the immune response.
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
Given the crucial role of reverse transcriptase in the viral life cycle, inhibitors of this enzyme have been explored for HTLV-1 therapeutics. Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine and tenofovir, have shown some efficacy in reducing viral loads in vitro and in clinical settings.
Immunomodulatory Therapies
Therapeutic strategies focusing on modulating the host immune response, such as the use of interferons and monoclonal antibodies, have shown promise in clinical trials. These therapies aim to boost the host's immune response against HTLV-1-infected cells.
Protease Inhibitors
Although less effective due to differences in the viral protease structure, some HIV-1 protease inhibitors have shown activity against HTLV-1. This class of drugs targets the maturation of viral proteins, thereby inhibiting the production of infectious virions.
Integrase Inhibitors
Integrase inhibitors, like raltegravir, target the integration of viral DNA into the host genome. These inhibitors have demonstrated potential in reducing viral replication and proviral loads in HTLV-1-infected cells.
Our Services
At our company, we offer comprehensive vaccine and therapy development services for HTLV-1 infection. Our team employs cutting-edge technologies to explore and develop novel therapeutic strategies.
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.
