AUTHOR=Liu Ying , Wen Zhiyuan , Carrion Ricardo , Nunneley Jerritt , Staples Hilary , Ticer Anysha , Patterson Jean L. , Compans Richard W. , Ye Ling , Yang Chinglai 

TITLE=Intradermal Immunization of EBOV VLPs in Guinea Pigs Induces Broader Antibody Responses Against GP Than Intramuscular Injection

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00304

DOI=10.3389/fmicb.2020.00304

ISSN=1664-302X

ABSTRACT=Ebolavirus (EBOV) infection causes severe hemorrhagic fever in humans with high mortality rates ranging from 30% to 80% as observed in different outbreaks.  Thus the development of safe and efficacious EBOV vaccines remains to be an important goal for biomedical research. We have shown in early studies that EBOV virus-like particles (VLPs) produced in insect cells are able to induce protective immune responses in mice against lethal EBOV challenge. In the present study, we investigated immune responses induced by Ebola VLPs via two different routes, intramuscular and intradermal immunizations, in guinea pigs. Analysis of antibody responses showed that similar levels of total IgG antibody responses against the EBOV glycoprotein (GP) were induced by the two different immunization methods.  However, further characterization showed that the EBOV GP-specific antibodies induced by intramuscular immunization were mainly of the IgG2 subtype whereas both IgG1 and IgG2 antibodies against EBOV GP were induced by intradermal immunization. In contrast, antibody responses against the EBOV matrix protein VP40 induced by intramuscular or intradermal immunizations exhibited similar IgG1 and IgG2 profiles. More interestingly, we found that the sites that the IgG1 antibodies induced by intradermal immunizations bind to in GP are different from those that bind to the IgG2 antibodies induced by intramuscular immunization.  Further analyses revealed that sera from all vaccinated guinea pigs exhibited neutralizing activity against Ebola GP-mediated HIV pseudovirion infection at high levels. Moreover, all EBOV VLP-vaccinated guinea pigs were protected from challenge with a high dose (1000 pfu) of guinea pig-adapted Ebola virus, while all control guinea pigs immunized with irrelevant VLPs succumbed to the challenge. The induction of both IgG1 and IgG2 antibody responses that recognized broader sites in GP by intradermal immunization of EBOV VLPs indicates that this approach may represent a more advantageous route of vaccination against virus infection.