Codelivery of CCR7 ligands as molecular adjuvants enhances the protective immune response against herpes simplex virus type 1
- PMID: 14610196
- PMCID: PMC262576
- DOI: 10.1128/jvi.77.23.12742-12752.2003
Codelivery of CCR7 ligands as molecular adjuvants enhances the protective immune response against herpes simplex virus type 1
Abstract
Humoral and cellular immunity, associated with long-term protective immunological memory, defines the efficacy of a given vaccine formulation. However, few vaccines achieve this target without the aid of a suitable adjuvant. Molecular adjuvants in vaccination against infectious agents offer a noninvasive means of enhancing the immune response against target antigens. To examine the potency of two beta-chemokines as immunomodulators, plasmid DNA encoding beta-chemokines CCL19 and CCL21 (CCR7L) was codelivered intranasally with plasmid DNA or recombinant vaccinia virus encoding herpes simplex virus (HSV) gB (HSV-gB) in a prime-and-boost vaccination strategy. This vaccination regimen increased serum and vaginal immunoglobulin G (IgG) and IgA, respectively, as well as the numbers of HSV-gB(498-505) peptide-specific gamma interferon-producing CD8(+) T cells. Distinctively, a high number of cytotoxic T lymphocytes was achieved when pCCR7L was applied at both prime and boost as opposed to omission of pCCR7L. A rapid-recall response was induced in the genital tract upon challenge with the HSV McKrae strain, affording a high level of protection and survival of vaccinated mice. Our results demonstrate that high innate immune kinetics and distribution of adaptive response induced in the nasal mucosa appears to be key factors in generating protective memory responses against HSV. Thus CCR7L expressed ectopically may serve as a molecular adjuvant to boost the immune response to a codelivered antigen in mucosal surfaces.
Figures
![FIG. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917001.gif)
![FIG. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917002.gif)
![FIG. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917003.gif)
![FIG. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917004.gif)
![FIG. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917005.gif)
![FIG. 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917006.gif)
![FIG. 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917007.gif)
![FIG. 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/262576/bin/jv2330917008.gif)
Similar articles
-
CCL19 and CCL28 Assist Herpes Simplex Virus 2 Glycoprotein D To Induce Protective Systemic Immunity against Genital Viral Challenge.mSphere. 2021 Apr 28;6(2):e00058-21. doi: 10.1128/mSphere.00058-21. mSphere. 2021. PMID: 33910988 Free PMC article.
-
Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of plasmid DNA expressing CCR7 ligands.Vaccine. 2001 Sep 14;19(32):4685-93. doi: 10.1016/s0264-410x(01)00241-9. Vaccine. 2001. PMID: 11535317
-
Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization.J Virol. 1997 Apr;71(4):3138-45. doi: 10.1128/JVI.71.4.3138-3145.1997. J Virol. 1997. PMID: 9060677 Free PMC article.
-
Recombinant herpes simplex virus type 1 (HSV-1) codelivering interleukin-12p35 as a molecular adjuvant enhances the protective immune response against ocular HSV-1 challenge.J Virol. 2005 Mar;79(6):3297-308. doi: 10.1128/JVI.79.6.3297-3308.2005. J Virol. 2005. PMID: 15731224 Free PMC article.
-
Understanding natural herpes simplex virus immunity to inform next-generation vaccine design.Clin Transl Immunology. 2016 Jul 29;5(7):e94. doi: 10.1038/cti.2016.44. eCollection 2016 Jul. Clin Transl Immunology. 2016. PMID: 27525067 Free PMC article. Review.
Cited by
-
The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics.Int J Mol Sci. 2023 Oct 1;24(19):14820. doi: 10.3390/ijms241914820. Int J Mol Sci. 2023. PMID: 37834268 Free PMC article. Review.
-
CCL28 Enhances HSV-2 gB-Specific Th1-Polarized Immune Responses against Lethal Vaginal Challenge in Mice.Vaccines (Basel). 2022 Aug 10;10(8):1291. doi: 10.3390/vaccines10081291. Vaccines (Basel). 2022. PMID: 36016177 Free PMC article.
-
CCL19 and CCL28 Assist Herpes Simplex Virus 2 Glycoprotein D To Induce Protective Systemic Immunity against Genital Viral Challenge.mSphere. 2021 Apr 28;6(2):e00058-21. doi: 10.1128/mSphere.00058-21. mSphere. 2021. PMID: 33910988 Free PMC article.
-
Cationic Dendrimer G2-S16 Inhibits Herpes Simplex Type 2 Infection and Protects Mice Vaginal Microbiome.Pharmaceutics. 2020 Jun 4;12(6):515. doi: 10.3390/pharmaceutics12060515. Pharmaceutics. 2020. PMID: 32512836 Free PMC article.
-
CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention.Front Cell Dev Biol. 2019 Oct 1;7:212. doi: 10.3389/fcell.2019.00212. eCollection 2019. Front Cell Dev Biol. 2019. PMID: 31632965 Free PMC article. Review.
References
-
- Badovinac, V. P., and J. T. Harty. 2003. Memory lanes. Nat. Immunol. 4:212-213. - PubMed
-
- Cyster, J. G. 1999. Chemokines and cell migration in secondary lymphoid organs. Science 286:2098-2102. - PubMed
-
- DiPaolo, R. J., and E. R. Unanue. 2002. Cutting edge: chemical dominance does not relate to immunodominance: studies of the CD4+ T cell response to a model antigen. J. Immunol. 169:1-4. - PubMed
-
- Dodge, I. L., M. W. Carr, M. Cernadas, and M. B. Brenner. 2003. IL-6 production by pulmonary dendritic cells impedes Th1 immune responses. J. Immunol. 170:4457-4464. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous