Herpes simplex virus (HSV) infection can cause severe recurrent disease in humans and establish lifelong latency in the host. Furthermore, it can significantly increase the risk of HIV infection and bring substantial psychosexual as well as physical morbidity to the patients. Several antiviral therapies are available for the control of its symptoms and spreading, but they can neither cure nor alter the nature of HSV infection. The development of an efficacious HSV vaccine is therefore necessitated for controlling the occurrence, transmission and recurrence of the infection. Those that have undergone clinical evaluation include subunit vaccines, attenuated live virus vaccines, replication defective virus vaccine, naked DNA vaccines and viral vector vaccines. Most of the above vaccine strategies have elicited protective immunity in animal models, but none has yet been effective in human beings. For all that, scholars have never stopped their exploration for an effective vaccine against the notorious virus. The authors present an overview of a few most promising candidate vaccines for the prevention and treatment of HSV infection.
Herpes Simplex ; prevention & control ; Herpes Simplex Virus Vaccines ; Humans

Changes in sexual behavior may constitute an important contribution to relative increase in genital herpes. Many research results suggest that HSV-2 plays a big part in the transmission of HIV infection. There is an urgent need to identify effective HSV-2 control measures in order to reduce HIV incidence. The detection of HSV-2-specific antibodies in serum is especially useful and reliable. During the past 2 decades, selective and specific inhibitors of replication have been developed. Such agents as acyclovir, valaciclovir and famciclovir, have reduced the time of healing and the possibility of virus excretion. Efforts have been made in different directions including the exploration of new targets for antiviral chemotherapy, the use of immunomodulators and the development of specific vaccines.
Adjuvants, Immunologic ; therapeutic use ; Antiviral Agents ; therapeutic use ; China ; epidemiology ; Herpes Genitalis ; diagnosis ; epidemiology ; therapy ; Herpes Simplex Virus Vaccines ; therapeutic use ; Humans

OBJECTIVETo construct eukaryotic expression plasmid IRES-gD-IL-2 which contains both HSV-1 glycoprotein D (gD) gene and IL-2 gene and to induce it to express in antigen presenting cell (APC) -- dendritic cells (DCs).

METHODSThe whole sequence of gD and IL-2 were amplified by PCR assay. After confirmation by PCR, double-enzyme digestion and sequencing, these genes were directly cloned into eukaryotic expression vector IRES, then were transfected into DCs. Western blotting was employed to identify the transcription and expression of gD gene.

RESULTSThe results of PCR and enzyme digestion showed that the recombinant expression plasmid contained correct fragments, and the transcription and expression of gD were confirmed by Western blotting.

CONCLUSIONThe recombinant expression vector IRES-gD-IL-2 was constructed, the results of the Western blotting showed that the recombinant protein could be identified by gD- specific antibody, therefore the protein has immunologic competence.

Blotting, Western ; Dendritic Cells ; metabolism ; Herpes Simplex Virus Vaccines ; immunology ; Humans ; Interleukin-2 ; genetics ; Plasmids ; Recombinant Fusion Proteins ; genetics ; immunology ; Vaccines, DNA ; immunology ; Viral Envelope Proteins ; genetics

Cholera toxin, which has been frequently used as mucosal adjuvant, leads to an irreversible activation of adenylyl cyclase, thereby accumulating cAMP in target cells. Here, it was assumed that beta2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since beta2-adrenergic agonists induce a temporary cAMP accumulation. To test this assumption, the present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB of herpes simplex virus (HSV) via intranasal (i.n.) route. We found that the i.n. co-administration of salbutamol enhanced gB-specific IgG and IgA responses in both systemic and mucosal tissues, but optimal dosages of co-administered salbutamol were required to induce maximal immune responses. Moreover, the mucosal co-delivery of salbutamol with HSV DNA vaccine induced Th2-biased immunity against HSV antigen, as evidenced by IgG isotypes and Th1/Th2-type cytokine production. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection. Therefore, these results suggest that salbutamol may be an attractive adjuvant for mucosal genetic transfer of DNA vaccine.
Adjuvants, Immunologic/*pharmacology ; Adrenergic beta-Agonists/immunology/*pharmacology ; Albuterol/immunology/*pharmacology ; Animals ; Antibodies, Viral/immunology ; Cercopithecus aethiops ; Cytokines/immunology ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Immunologic ; Herpes Simplex/immunology/*prevention & control ; Herpes Simplex Virus Vaccines ; Immunity, Mucosal/*drug effects/immunology ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; Mice ; Simplexvirus/*immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; Vaccines, DNA/*immunology/pharmacology ; Vero Cells ; Viral Envelope Proteins/immunology

To construct an HSV-1 vector vaccine carrying HIV-1 antigens, HIV-1 gp160, gag, protease and the expression elements were chained together, and then inserted into the internal inverted repeat sequence region of HSV-1 by bacterial artificial chromosome technology. Firstly, HIV-1 gp160 (including type B and C), gag and protease genes were cloned into pcDNA3 in series to generate the pcDNA/gBgp and pcDNA/gCgp, then the recombinant plasmids were transfected into 293FT cells, and HIV-1 antigen was detected from transfected cells by Western blotting. Then the expression cassettes from pcDNA/gBgp and pcDNA/gCgp, comprising HIV-1 antigen genes and expression elements, were cloned into pKO5/BN to generate the shuttle plasmids pKO5/BN/gBgp and pKO5/BN/gCgp. The shuttle plasmids were electroporated into E. coli cells that harbor an HSV-BAC, the recombinant bacteria were screened, and the recombinant DNA was extracted and transfected into Vero cells. The recombinant virus was purified through picking plaques, the virus' DNAs were identified by Southern blotting; HIV-1 antigen was detected from the recombinant HSV-1 infected cells by Western blotting, and the virus' replication competent was analyzed. As the results, gp160 and gag proteins were detected from 293FT cells transfected with pcDNA/gBgp and pcDNA/gCgp by Western blotting. The recombinant bacteria were generated from the E. coli electroporated with pKO5/BN/gBgp or pKO5/BN/gCgp. The recombinant HSV was purified from the Vero cells transfected with the recombinant DNA, the unique DNA fragment was detected from the genome of recombination HSV by Southern blotting; gp120 and gp41 were detected from the infected cells by Western blotting, and the recombinant HSV retained replication competent in mammalian cells. The results indicate that the recombinant HSV carrying HIV-1 gp160, gag and protease genes was generated, the virus retains replication competent in mammalian cells, and could be used as a replicated viral vector vaccine.
Animals ; Cercopithecus aethiops ; Chromosomes, Artificial, Bacterial ; DNA, Recombinant ; genetics ; DNA, Viral ; genetics ; Escherichia coli ; HIV Antigens ; genetics ; immunology ; HIV Envelope Protein gp160 ; genetics ; immunology ; HIV Protease ; genetics ; immunology ; Herpes Simplex Virus Vaccines ; immunology ; Herpesvirus 1, Human ; physiology ; Plasmids ; Transfection ; Vero Cells ; Virus Replication ; gag Gene Products, Human Immunodeficiency Virus ; genetics ; immunology