Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens

Abstract

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events. In our earlier studies, we made a surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses and that immunizing mice with a non-replicating, non-recombinant adenovirus vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. In this work, we further demonstrate antibody cross-reactivity between Ad and HCV in vivo. We also extend this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive immunity can (a) accommodate the making of dual-pathogen vaccines, (b) play an important role in the natural course of HCV infection and (c) provide a plausible answer to many unexplained questions regarding immunity to HCV.

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

“…Adenovirus vectors based on human serotype 5 of species C are widely used as gene delivery vehicles that enabled high-titer production and highly efficient gene transfer into targeted cells. 27 The oncolytic adenovirus carrying therapeutic genes has shown to exert promising antitumor effects on different types of cancers. [28][29][30] In our study, we used the AdEasy system 31 to construct new recombinant adenovirus Ad-RGD-Survivin-ZD55-miR-143: replacing the original E1A promoter with tumor-specific Survivin promoter could transcriptionally control viral replication; deleting the E1B-55kDa region could lose the ability to replicate in normal cells; and inserting an RGD motif into the HI loop of the adenovirus knob could elevate the infection efficiency.…”

Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine

“…Another possibility is that there may be heterologous immunity due to a protein in SARS CoV-2 that is homologous to a protein in Mycobacterium bovis . Such heterologous immunity has been documented between other pathogens, such as adenovirus and hepatitis C virus [ 10 ]. The presence of such immunity between a SARS-CoV-2 capsid protein and a protein of Mycobacterium bovis would allow for a much stronger and specific immunity against the virus subsequent to BCG vaccination.…”

Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections

“…It remains to be investigated whether Ad-specific effector-memory T cells provide the immediate defense when exposed to infecting HCV, and whether they form at least a partial basis for the 15–30% spontaneous clearance of HCV observed in humans. In a follow up report, we demonstrated that cross-reactive cellular and humoral immune responses against HCV antigens core, NS3, and NS5 are also induced upon immunization with various recombinant Ads containing antigens from HCV, Mycobacterium tuberculosis , HIV, and EBOV (94). Intriguingly, the nature of the transgene antigen had a significant impact on the levels of cross-reactive immunity induced against HCV antigens (94).…”

“…In a follow up report, we demonstrated that cross-reactive cellular and humoral immune responses against HCV antigens core, NS3, and NS5 are also induced upon immunization with various recombinant Ads containing antigens from HCV, Mycobacterium tuberculosis , HIV, and EBOV (94). Intriguingly, the nature of the transgene antigen had a significant impact on the levels of cross-reactive immunity induced against HCV antigens (94). It is possible that Ad also has cross-reactivity with other pathogens, but this has not been explored yet.…”