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Table 4 Characteristics of recombinant-vaccina-virus vaccine studies

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

Author

Year

Country

Type of study

Host

Vaccine immunogen content

Vaccine dose

Route

Prescribed number

Laboratory method

Main findings

Shida, H

1987

Japan

in vivo

rabbits

The envelope gene of HTLV-I in the vaccinia virus hemagglutinin (HA) gene

NA

ID

once

IFA

HA gene is a useful site to accept and express foreign genes/ A single inoculation of the recombinant virus-induced antibodies to the env proteins of HTLV-I in rabbits and had a protective effect against HTLV-I infection

Shida, H

1988

Japan

in vivo

Japan albino rabbits, each weighing 1.8 to 2.3 kg and 5-week-old male DDY mice

HTLV-1 envelope gene

NA

IP/IC

once

IFA

LC16mO is a good candidate as a vector for vaccination

Ford, C. M

1992

USA

in vivo

Balb/c, A/J, and C57BU6 strains of mice

RVV El expressed the native HTLV-I envelope proteins gp46 (surface protein) and gp21 (transmembrane protein)

RVV E2 expressed the envelope precursor with the proteolytic cleavage site deleted

RVV E3 construct expressed only the external surface glycoprotein (gp46)

NA

intraperitoneal

NA

Southern blot, Immunofluorescence assays, Radioimmunoprecipitation assays, ELISA, Western blot assays

Balb/c mice responded poorly to immunization with all of the three RVV constructs. C57BU6 mice produced neutralizing antibodies in response to immunization with all three constructs, whereas A/J mice developed neutralizing antibodies only when immunized with the RVV El s construct. The results indicate that the humoral immune responses depend on the form of HTLV-I envelope proteins expressed by each RVV

Hakoda, E

1995

Japan

in vivo

Japanese white rabbits

env gene in the hemagglutinin locus, WR-SFBSenv

\(1\times10^{8}\) plaque-forming units of recombinant or control virus at 3 sites on the back

intradermally

one time in 3 sites in the back of tabbits

PCR, western bloth, ELISA, plaque-reduction assay

Incapable of inducing neutralizing antibodies

Arp, J

1996

USA

in vitro

baculovirus non-fusion vector system

gp46

NA

NA

NA

PCR, ELISA, western blot, y immunofluorescence assays

Maintenance of highly conserved conformational epitopes in the recombinant HTLV-1 envelope protein structure

Ibuki, K

1997

Japan

in vivo

cynomolgus monkeys (Macaca fascicularis)

HTLV-I envelope (Env) gp46

Two monkeys: 3.10 p.f.u. of WR-SFB5env

three monkeys: \(3.10^{8}\) p.f.u. of HA − VV

ID

1

western blot, PCR, particle agglutination, IFA

Neither HTLV-I antigen nor HTLV-I proviruses were detected/ Single immunization with WR-SFB5env elicited long-lived anti-Env antibodies as well as Env-specific CTL activity/ Gp46 expression alone was sufficient for protection

Kazanji, M

2001

France

in vivo

male squirrel monkeys

env/gag

In the initial protocol, three monkeys \(10^{8}\) PFU of NYVAC / Six months after the last administration of NYVAC-env, two of the three vaccinated monkeys were boosted with 500 mg of the naked DNA immunogen CMV-env-LTR, The third monkey and the control were injected with a naked DNA vector containing the b-galactosidase gene (CMV-bgal)

In the second immunization protocol, three monkeys 500 mg of the DNA immunogen CMV-env-LTR and the control monkey was injected with the CMV-bgal vector. Six months later,the three vaccinated monkeys received a series of three booster injections, separated by 1-month intervals, of 108 PFU of the NYVAC-based candidate vaccine containing the HTLV-1 env and gag genes. The control monkey received 108 PFU of NYVAC-RG at the same times

IM

protocol A: (3 monkeys) 0, 1, and 3 months (108 PFU of NYVAC containing the HTLV-1 env gene)

Six months after the last administration of NYVAC-env, two of the three vaccinated monkeys were boosted with 500 mg of the naked DNA immunogen CMV-env-LTR intramuscularly into the tibialis anterior muscle

protocol B: (3 monkeys) 500 mg of the DNA immunogen CMV-env-LTR. Six months later, received a series of three booster injections, separated by 1-month intervals, of 108 PFU of the NYVAC-based candidate vaccine contain ing the HTLV-1 env and gag genes

ELISA, PCR, western blot

protocol A: With the first immunization protocol, no anti-bodies against HTLV-1

HTLV-1 Env gp46 was stimulated in all of the three immu nized monkeys and a lesser response was stimulated in the control monkey protocol B: did not induce detectable levels of antibodies against HTLV-1

In the lymphocyte proliferation test performed 1 month after boosting, high-level, specific responses were detected in the three immunized animals against both recombinant Env gp46 protein and Gag peptides but not in the control monkey

Sugata, Kenji

2015

Japan

in vivo

Ly5.1 C57BL/6 mice, rhesus monkeys

HTLV-1 basic leucine zipper (bZIP) factor (HBZ) or Tax

Each animal received a dose of 107 plaque forming units of rVV in 10 mL of viral suspension

skin sacrifation

In mice, 4 weeks after the first vaccination, 5 booster vaccinations were administered every 3 weeks

In monkeys, booster vaccinations were repeated every 4 weeks. PBMCs from monkeys were obtained every 2 weeks

ELISPOT, immunoblotting

Increased survival of the lymphoma cell–inoculated mice/ Induction of specific T-cell responses to HBZ and Tax in HTLV-1–infected rhesus monkeys/ A candidate peptide (HBZ157-176) for vaccine development was identified/ Dendritic cells pulsed with this peptide could generate HBZ-specific CTLs from human CD81 T cells