Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania

被引：96

作者：

Bakari, Muhammad ^{[1
]}

Aboud, Said ^{[2
,4
]}

Nilsson, Charlotta ^{[4
,5
]}

Francis, Joel ^{[6
]}

Buma, Deus ^{[8
]}

Moshiro, Candida ^{[3
]}

Aris, Eric A. ^{[7
]}

Lyamuya, Eligius F. ^{[2
]}

Janabi, Mohamed ^{[7
]}

Godoy-Ramirez, Karina ^{[5
]}

Joachim, Agricola ^{[2
,4
]}

Polonis, Victoria R. ^{[9
]}

Brave, Andreas ^{[5
]}

Earl, Patricia ^{[10
]}

Robb, Merlin ^{[11
]}

Marovich, Mary ^{[9
]}

Wahren, Britta ^{[4
,5
]}

Pallangyo, Kisali ^{[1
]}

Biberfeld, Gunnel ^{[4
,5
]}

Mhalu, Fred ^{[2
]}

Sandstrom, Eric ^{[12
]}

机构：

[1] MUHAS, Dept Internal Med, Dar Es Salaam, Tanzania

[2] MUHAS, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania

[3] MUHAS, Dept Epidemiol & Biostat, Dar Es Salaam, Tanzania

[4] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden

[5] Swedish Inst Communicable Dis Control SMI, Solna, Sweden

[6] NIMR, Dar Es Salaam, Tanzania

[7] MNH, Dept Internal Med, Dar Es Salaam, Tanzania

[8] MNH, Dept Pharm, Dar Es Salaam, Tanzania

[9] WRAIR, Rockville, MD USA

[10] NIAID, NIH, Bethesda, MD 20892 USA

[11] Henry M Jackson Fdn, Rockville, MD USA

[12] Karolinska Inst, Sodersjukhuset, Stockholm, Sweden

来源：

VACCINE | 2011年 / 29卷 / 46期

基金：

瑞典研究理事会;

关键词：

HIV vaccine; DNA prime; MVA boost; DAR-ES-SALAAM; CD8(+) T-CELL; PHASE-1; SAFETY; IMMUNOGENICITY EVALUATION; POLICE OFFICERS; VACCINE TRIAL; DOUBLE-BLIND; ANKARA MVA; CLADE-C; CANDIDATE;

D O I：

10.1016/j.vaccine.2011.08.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. Methods: Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally (id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B. C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0,4 and 12. Recombinant MVA (10(8) pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. Results: The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-gamma ELISpot responses to 3Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-gamma ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-gamma/IL-2 production showed both CD8(+) and CD4(+) T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. This vaccine approach is safe and highly immunogenic. Low dose. id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：8417 / 8428

页数：12

共 55 条

[1] Evaluation of HIV antibody and antigen/antibody combination ELISAs for use in an alternative confirmatory HIV testing strategy in Dar es Salaam, Tanzania [J].