Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies

Abstract

Background Numerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for status assessment and strategic planning of future preventative actions to reduce HTLV-1 infection and its consequences would be essential. Methods MEDLINE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through March 27, 2022. All original articles focusing on developing an HTLV-1 vaccine candidate were included. Results A total of 47 studies were included. They used a variety of approaches to develop the HTLV-1 vaccine, including DNA-based, dendritic-cell-based, peptide/protein-based, and recombinant vaccinia virus approaches. The majority of the research that was included utilized Tax, Glycoprotein (GP), GAG, POL, REX, and HBZ as their main peptides in order to develop the vaccine. The immunization used in dendritic cell-based investigations, which were more recently published, was accomplished by an activated CD-8 T-cell response. Although there hasn't been much attention lately on this form of the vaccine, the initial attempts to develop an HTLV-1 immunization depended on recombinant vaccinia virus, and the majority of results seem positive and effective for this type of vaccine. Few studies were conducted on humans. Most of the studies were experimental studies using animal models. Adenovirus, Cytomegalovirus (CMV), vaccinia, baculovirus, hepatitis B, measles, and pox were the most commonly used vectors. Conclusions This systematic review reported recent progression in the development of HTLV-1 vaccines to identify candidates with the most promising preventive and therapeutic effects.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

“…A therapeutic vaccine for HTLV-1 should be based on the control of the proviral load by Th-1 response [ 13 , 39 ], since a high proviral load is associated with illnesses in infected individuals [ 40 ]. As proposed by MacNamara and colleagues [ 23 ] a lower proviral load is observed in individuals expressing MHC-I alleles that bind strongly to HBZ antigens, inducing a robust T CD8 + response that would regulate the proliferation of infected cells, consequently leading to asymptomatic conditions.…”

“…As proposed by MacNamara and colleagues [ 23 ] a lower proviral load is observed in individuals expressing MHC-I alleles that bind strongly to HBZ antigens, inducing a robust T CD8 + response that would regulate the proliferation of infected cells, consequently leading to asymptomatic conditions. Also, effective immunogens against viral infections should trigger cellular and humoral responses, while T CD4 + cells stimulate antibody production and sustain the effector functions of CTLs, which induces clearance of infected cells through inflammatory mediators [ 13 , 41 ]. In the present study, it was possible to observe the activation of both T CD4 + and T CD8 + lymphocytes in immunized mice after in vitro stimulation with HBZ peptides, similar to the findings of Sugata et al [ 17 ].…”

“…Based on the knowledge advances in the HTLV-host interaction and in the biotechnology recent systematic reviews and reports showed a plethora of approaches for HTLV-1 vaccine candidates: viral like particles vectors and viral vectors (Vaccinia virus, Adenovirus and Sendai virus), dendritic cell and peptide-based vaccines, recombinant single proteins or multiepitope proteins expressed in different systems including molecules encapsulated using nanotechnology [ 9 – 13 ]. Of great interest 15 peptide stretches (from Gag and Gag-Pro-Pol polyproteins, Tax-1 and gp62) were presented from an epitope platform for HTLV-1 vaccine development of uniquely viral non-human pentapeptides to avoid cross-reaction, generating safe immunization based on peptides and mRNA [ 14 ].…”

Заболевания, Ассоциированные С Т-Лимфотропным Вирусом Типа 1 Человека (HTLV-1)

“…К настоящему времени предложено несколько профилактических мер, а именно: дородовой скрининг и обследование доноров крови и органов. Однако споры об экономической эффективности этих мер не утихают, что связано с географической гетерогенностью эндемичных по HTLV-1-инфекции территорий [79,80].…”

“…Разработка эффективной вакцины позволит ограничить или даже предотвратить передачу HTLV-1, а также снизить вирусную нагрузку у инфицированных пациентов и тем самым вероятность развития HTLV-1-ассоциированных заболеваний. На сегодня известно несколько типов HTLV-1-вакцин, находящихся на разных этапах испытаний: пептидно-белковые, инкапсулированные и содержащие адъювант; полиэпитопные; на основе ДНК, дендритных клеток, рекомбинантного вируса осповакцины и другие [79,80].…”