Editing DNA vaccine (section)

=== Vaccine insert design ===

Immunogens can be targeted to various cellular compartments to improve antibody or cytotoxic T-cell responses. Secreted or [[plasma membrane]]-bound antigens are more effective at inducing antibody responses than [[cytosolic]] antigens, while [[cytotoxic T-cell]] responses can be improved by targeting antigens for cytoplasmic degradation and subsequent entry into the [[major histocompatibility complex]] (MHC) class I pathway.<ref name=Robinson2000 /> This is usually accomplished by the addition of [[N-terminal]] [[ubiquitin]] signals.<ref name=Rodriguez1997>{{cite journal | vauthors = Rodriguez F, Zhang J, Whitton JL | title = DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction | journal = Journal of Virology | volume = 71 | issue = 11 | pages = 8497–8503 | date = November 1997 | pmid = 9343207 | pmc = 192313 | doi = 10.1128/JVI.71.11.8497-8503.1997 }}</ref><ref name=Tobery1997>{{cite journal | vauthors = Tobery TW, Siliciano RF | title = Targeting of HIV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization | journal = The Journal of Experimental Medicine | volume = 185 | issue = 5 | pages = 909–920 | date = March 1997 | pmid = 9120397 | pmc = 2196169 | doi = 10.1084/jem.185.5.909 }}</ref><ref>{{cite journal | vauthors = Huebener N, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, Gaedicke G, Lode HN | display-authors = 6 | title = A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity | journal = Molecular Cancer Therapeutics | volume = 7 | issue = 7 | pages = 2241–2251 | date = July 2008 | pmid = 18645033 | doi = 10.1158/1535-7163.MCT-08-0109 | doi-access =  | s2cid = 35652424 | author-link8 = Lode HN, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, Gaedicke G, Lode HN }}</ref>

The [[protein conformation|conformation]] of the protein can also affect antibody responses. "Ordered" structures (such as viral particles) are more effective than unordered structures.<ref name=Wunderlich2000>{{cite journal | vauthors = Wunderlich G, Moura IC, del Portillo HA | title = Genetic immunization of BALB/c mice with a plasmid bearing the gene coding for a hybrid merozoite surface protein 1-hepatitis B virus surface protein fusion protects mice against lethal Plasmodium chabaudi chabaudi PC1 infection | journal = Infection and Immunity | volume = 68 | issue = 10 | pages = 5839–5845 | date = October 2000 | pmid = 10992493 | pmc = 101545 | doi = 10.1128/IAI.68.10.5839-5845.2000 }}</ref> Strings of minigenes (or MHC class I [[epitopes]]) from different pathogens raise cytotoxic T-cell responses to some pathogens, especially if a TH epitope is also included.<ref name=Robinson2000 />