Journal of eISSN: 2373-4469 JIG

Investigative Genomics
Mini Review
Volume 2 Issue 3

Recent advances and current status of gm-Csf as an adjuvant in DNA vaccines for viral diseases

Chandra Somasundaram
University of Houston- Victoria, Texas Biomedical Institute, Missouri City, USA
Received: May 31, 2015 | Published: June 16, 2015

Correspondence: Chandra Somasundaram, University of Houston-Victoria, Texas Biomedical Institute, Missouri City, Texas, USA, Email

Citation: Somasundaram C . Recent advances and current status of gm-Csf as an adjuvant in DNA vaccines for viral diseases. J Investig Genomics. 2015;2(3):54‒56. DOI: 10.15406/jig.2015.02.00025

Abstract

Here, I update the recent advances and current status of Granulocyte macrophage colony-stimulating factor (GM-CSF), since we have reported for the first time that porcine GM-CSF gene in a DNA vaccine formulation exerted immuno-adjuvant and protective effects against Aujeszky's (Pseudorabies)viral disease to the natural host pigs with a single vaccination. GM-CSF has been broadly used as an adjuvant in preclinical DNA vaccine studies for cancer and viral diseases. Currently, GeoVax Labs, Inc. reported a recombinant HIV vaccine (GEO-D03) that co-expresses the human GM-CSF and non-infectious HIV-1 virus-like particles (VLPs) is being evaluated in HIV infected young adults in several Phase I studies (NCT01571960). In addition, we summarized here the outcomes of the use of GM-CSF in DNA vaccine for other viral diseases. Further, phase 3 studies reported that GM-CSF showed an improvement in patient outcome when applied in combination with suitable anti-tumor vaccines. However, GM-CSF in excessive levels may expand myeloid suppressor cells that were shown to dampen adaptive immune responses.

Keywords: granulocyte macrophage colony-stimulating factor, gm-Csf, genetic adjuvant, DNA vaccine, viral disease, cancer, clinical trial

Abbreviations

GM-CSF, granulocyte macrophage colony-stimulating factor; HIV, human immunodeficiency virus; SIV, simian immunodeficiency virus

Introduction

Here, I update the recent advances and current status of Granulocyte macrophage colony-stimulating factor (GM-CSF), since we have reported for the first time1,2 that a DNA vaccine formulation with porcine GM-CSF gene exerted immuno-adjuvant effects and protected the natural host pigs against Aujeszky's (Pseudorabies) viral disease with single vaccination. The hematopoietic cytokine GM-CSF has been shown as an efficient adjuvant in DNA vaccine preclinical studies for cancer and viral diseases. Xiang Z et al.3 first reported that GM-CSF is a genetic adjuvant for DNA vaccine.

GM-CSF as a genetic adjuvant for HIV DNA vaccine in human clinical trials

A recombinant HIV vaccine (GEO-D03) that co-expresses the human GM-CSF and non-infectious HIV-1 virus-like particles (VLPs) is being currently evaluated in HIV infected young adults in several Phase I studies (NCT01571960- 2015).4,5 This trial will determine whether this vaccine will provide excellent protection in humans as in macaques by simian immunodeficiency virus (SIV)-prototype (NCT01909414-2013).6 Lai et al.7 2011 reported that the SIV vaccine co-expressing GM-CSF achieved significantly higher reduction in risk of infection and protected more SIV challenged macaques in preclinical studies. In addition, this vaccine elicited both anti-viral T cells and antibody. The vaccine-induced prevention of infection was shown to increase from 25% to 71% in the presence of GM-CSF.7 The Outcomes of the use of GM-CSF as genetic adjuvant in DNA vaccine for other viral diseases is given in Table 1.

Virus

Efficacy/Outcome of GM-CSF

Reference

Porcine Circovirus Type-2

Pigs immunized with Cap-GM-CSF subunit vaccine showed significantly higher levels of PCV2-specific antibodies and neutralizing antibodies and higher average daily weight gain than pigs receiving immunized with the Cap subunit vaccine and a commercial vaccine (Ingelvac CircoFLEX; P<0.05) after wild-type PCV2 challenge.

8

Flaviviridae Virus

Reported as complex and diverse, ranging from enhancement to suppression, depending on the immunogen of Flaviviridae virus DNA vaccine candidates.

9

Simian ImmunoDeficiency Virus

The co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% to 71% in simian immunodeficiency virus in macaques.

7

GEO-D03, a DNA vaccine that expresses human GM-CSF and non-infectious HIV-1 virus-like particles .entered into human trials.

4

HIV/AIDS

A phase 1 study of the safety and immunogenicity of DNA/MVA immunizations with co-expressed GM-CSF in HIV-1 infected young adults with suppressed viremia on HAART.

5,6

Foot and Mouth Disease

Efficacy of the DNA vaccine with GM-CSF was improved further in reducing the clinical disease and virus excretions by electroporation.

10

Japanese Encephalitis Virus

Reported no protection

11

HIV

Induced long-lived humoral and cell mediated immune memory responses.

12

Dengue Virus

DV1 challenged mice showed long-term IgG response, strong cytotoxic T lymphocyte activity, produced high levels of splenocyte-secreted interferon-γ and interleukin-2 and sufficient protection after immunization with pCAG-DV1-GM-CSF immunization than pCAG-DV1/E alone

13

Induced stronger immunogenicity and protection from virus challenge in Aotus monkeys.

14

Influenza Virus

GM-CSF gene enhanced systemic and mucosal immunogenicity of the HA DNA vaccine in Rhesus macaque

15

Hepatitis B Virus

HBV-S gene fused with GM-CSF strengthened the immune effects of the HBV DNA vaccine in HBV-transgenic mice

16

Bronchitis Virus

pVAX-chGM-CSF and pVAX-S1 provided more protection against IBV challenge in chickens than pVAX-S1 vaccination alone.

17

Feline Immuno Deficiency Virus

Preserved global CD4 T lymphocyte function after the challenge..

18

Porcine Reproductive and Respiratory Syndrome Virus

Significantly enhanced the humoral and cellular immune responses and protection against PRRSV challenge in pigs

19

Hepatitis C Virus

Reported no change in the Th1/Th2 balance as compared with simultaneous IL-23 administration.

20

Co-immunization with Flt3-L and GM-CSF shown promise in the development of an effective
antiviral HCV vaccine

21

Simian-Human Immuno Deficiency Virus

Enhanced IgA response was associated with the best protection, but did not achieve significance.

22

HIV-1 Gag

Demonstrated strong antibody and CTL responses and a protective response against infection with recombinant vaccinia virus expressing HIV-1 Gag.

23

Equine Herpes Virus

DNA vaccine with GM-CSF, formulated in DMRIE-DOPE significantly improved virus neutralizing antibody responses to EHV-1.

24

HIV-1 Env

The adjuvant treated group showed significantly better control to the challenge than the non-GMCSF group.

25

Bicistronic DNA vaccines containing GM-CSF elicited remarkably potent CD4(+) T cell responses

26

Aujeszky's (Pseudorabies) Viral Disease.

We demonstrated that the Porcine GM-CSF gene in a DNA vaccine formulation exerted immuno-adjuvant and protective effects with single vaccination in the natural host pigs against Aujeszky's disease.

1

Table 1 Efficacy and outcomes of GM-CSF as genetic adjuvant in DNA vaccines for viral diseases

Use of GM-CSF in cancer

GM-CSF was found the most efficient adjuvant for cancer cell vaccines in early preclinical screens of retroviral-expressed cytokines.27 Further, the ability of the fused GM-CSF to elicit anti-tumor immune responses and boost vaccine efficiency is found in the first licensed cancer vaccine, Provenge.28 Despite, a number of studies demonstrating cytokines can act as adjuvants in tumor vaccines, the cost prevent their widespread use, except for the GM-CSF. More recently, GM-CSF has shown improved patient outcome in phase 3 studies when applied in combination with suitable anti-tumor vaccines.29 In addition, GM-CSF is licensed to use as an adjuvant in a fusion protein for a dendritic cell therapy for prostate cancer and for recovery and replacement of white blood cells following bone marrow transplantation and chemotherapy.30 However, GM-CSF in excessive levels may expand myeloid suppressor cells that were shown to dampen adaptive immune responses.31‒33

Acknowledgements

None.

Conflict of interest

Author declares that there is no conflict of interest.

References

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