Long-term memory B-cell responses in recipients of candidate human immunodeficiency virus type 1 vaccines

ABSTRACT We investigated long-term memory and recall cellular immune responses to human immunodeficiency virus type 1 (HIV-1) Env and Gag proteins elicited by recombinant vesicular stomatitis viruses (VSVs) expressing Env and Gag. More than 7 months after a single vaccination with VSV-Env, ∼6% of CD8+ splenocytes stained with major histocompatibility complex class I tetramers containing the Env p18-I10 immunodominant peptide and showed a memory phenotype (CD44Hi). The level of tetramer-positive cells in memory was about 14% of the peak primary response. Recall responses elicited in these mice 5 days after boosting with a heterologous recombinant vaccinia virus expressing HIV-1 Env showed that 40 to 45% of CD8+ splenocytes were tetramer positive and activated (CD62LLo), and these cells produced gamma interferon after stimulation with Env peptide, indicating that they were functional. Five months after the boost, the long-term memory cell population (tetramer positive, CD44Hi) constituted 30% of the CD8+ splenocytes. Recall responses to HIV-1 Gag were examined in mice primed with VSV recombinants expressing HIV-1 Gag protein and boosted with a vaccinia virus recombinant expressing Gag. Using this protocol, we found that ∼40% of CD8+ splenocytes were activated (CD62LLo) and specific for a Gag immunodominant peptide (tetramer positive). The high-level Gag recall response elicited by the vaccinia virus-Gag was greater than that obtained by boosting with a VSV-Gag vector with a different VSV glycoprotein. The corresponding levels of CD44Hi memory cells were also higher long after boosting with vaccinia virus-Gag than after boosting with a glycoprotein exchange VSV-Gag. Our results show that VSV vectors elicit high-level memory CTL responses and that these can be amplified as much as six- to sevenfold using a heterologous boosting vector.

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Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro

Cellular and Molecular Immunology ◽

10.1038/cmi.2017.48 ◽

2017 ◽

Vol 15 (10) ◽

pp. 917-933 ◽

Cited By ~ 5

Author(s):

Jacobo Lopez-Abente ◽

Adrián Prieto-Sanchez ◽

Maria-Ángeles Muñoz-Fernandez ◽

Rafael Correa-Rocha ◽

Marjorie Pion

Keyword(s):

Human Immunodeficiency Virus ◽

B Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Regulatory B Cell ◽

Immunodeficiency Virus

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Progressive B Cell Apoptosis and Expression of Fas Ligand during Human Immunodeficiency Virus Type 1 Infection

AIDS Research and Human Retroviruses ◽

10.1089/aid.1997.13.1031 ◽

1997 ◽

Vol 13 (12) ◽

pp. 1031-1038 ◽

Cited By ~ 44

Author(s):

ASTRID SAMUELSSON ◽

ANDERS SÖNNERBORG ◽

NICOLE HEUTS ◽

JOAKIM CÖSTER ◽

FRANCESCA CHIODI

Keyword(s):

Human Immunodeficiency Virus ◽

B Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cell Apoptosis ◽

Fas Ligand ◽

Immunodeficiency Virus

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Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

Journal of General Virology ◽

10.1099/vir.0.80481-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 349-354 ◽

Cited By ~ 35

Author(s):

Eva K. L. Nordström ◽

Mattias N. E. Forsell ◽

Christina Barnfield ◽

Eivor Bonin ◽

Tomas Hanke ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Dna Vaccine ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Semliki Forest Virus ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

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