Chimeric vaccine composed of viral peptide and mammalian heat‐shock protein 60 peptide protects against West Nile virus challenge

Abstract

Summary The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public‐health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B‐cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat‐shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458‐Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431‐Ep15, a control conjugate, were not protected. The chimeric p458‐Ep15 peptide induced WNV‐specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon‐γin vitro. Challenge of chimeric peptide‐immunized mice considerably enhanced WNV‐specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

The HSP60 immune system network

“…Defined multi-component vaccines conjugated to peptide p458 were found to induce IgG antibodies to otherwise poorly immunogenic capsular polysaccharide antigens of salmonella [94], pneumococci [27,95], and meningococci [96]; these vaccines were found to be effective even without added adjuvants. The HSP60 peptide was also able to enhance the immunogenicity of peptides from viruses such as cytomegalovirus [97] and West Nile virus [98]. Thus, HSP60 functions as the body's natural adjuvant [26], probably as a result of its ability to activate the innate and the adaptive immune response.…”

Leptin-based adjuvants: An innovative approach to improve vaccine response

“…It is a natural ligand for TLR2 and TLR4 and, depending on its concentration, can act as a pro- or an anti-inflammatory mediator. Furthermore, it has previously been found to enhance immune response to peptides from West Nile virus [80] and cytomegalovirus [81]. It is currently unknown if TUDCA and 4-PBA could be used as effective adjuvants; however, their involvement in leptin sensitivity and immune function (TUDCA only), as well as the efficacy of other chaperones (i.e., HSP60) as vaccine adjuvants, make them promising candidates.…”

Hsp65-Producing Lactococcocus lactis Prevents Antigen-Induced Arthritis in Mice

“…Treated individuals presented higher frequencies of Foxp3 + CD4 + T cells and higher expression levels IL-10 than the placebo group, and none of them presented compromised immune response to tetanus toxin (23). Furthermore, reactivity to HSP60 can be related to protection against several different infectious agents (49)(50)(51).…”