Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

Autor: Andrew G. Diamos, Tsafrir S. Mor, Hugh S. Mason, Qiang Chen, Jacquelyn Kilbourne, Mary D. Pardhe, Haiyan Sun, Lydia R. Meador, Joseph G. L. Hunter
Rok vydání: 2019
Předmět:
HBc
hepatitis B core antigen
Recombinant immune complex
Plant-made vaccine
medicine.medical_treatment
030231 tropical medicine
ZE3
Zika envelope domain III
Antigen-Antibody Complex
Antibodies
Viral
ZIKV
Zika virus
Neutralization
Article
Envelope protein
Zika virus
03 medical and health sciences
0302 clinical medicine
N-RIC
N-terminal antigen fusion RIC
Virus-like particle
Antigen
Pregnancy
C-RIC
C-terminal fusion RIC
hemic and lymphatic diseases
medicine
Humans
030212 general & internal medicine
Vaccines
Virus-Like Particle
General Veterinary
General Immunology and Microbiology
biology
Zika Virus Infection
Immunogenicity
Public Health
Environmental and Occupational Health
Antibody titer
ADE
antibody-dependent enhancement
Zika Virus
biology.organism_classification
Virology
Antibodies
Neutralizing
Immune complex
3. Good health
RIC
recombinant immune complex
Infectious Diseases
Viral Envelope
VLP
virus-like particle
Molecular Medicine
Female
Adjuvant
Zdroj: Vaccine
ISSN: 1873-2518
Popis: Zika virus (ZIKV) reemergence poses a significant health threat especially due to its risks to fetal development, necessitating safe and effective vaccines that can protect pregnant women. Zika envelope domain III (ZE3) has been identified as a safe and effective vaccine candidate, however it is poorly immunogenic. We previously showed that plant-made recombinant immune complex (RIC) vaccines are a robust platform to improve the immunogenicity of weak antigens. In this study, we altered the antigen fusion site on the RIC platform to accommodate N-terminal fusion to the IgG heavy chain (N-RIC), and thus a wider range of antigens, with a resulting 40% improvement in RIC expression over the normal C-terminal fusion (C-RIC). Both types of RICs containing ZE3 were efficiently assembled in plants and purified to >95% homogeneity with a simple one-step purification. Both ZE3 RICs strongly bound complement receptor C1q and elicited strong ZE3-specific antibody titers that correlated with ZIKV neutralization. When either N-RIC or C-RIC was codelivered with plant-produced hepatitis B core (HBc) virus-like particles (VLP) displaying ZE3, the combination elicited 5-fold greater antibody titers (>1,000,000) and more strongly neutralized ZIKV than either RICs or VLPs alone, after only two doses without adjuvant. These findings demonstrate that antigens that require a free N-terminus for optimal antigen display can now be used with the RIC system, and that plant-made RICs and VLPs are highly effective vaccines targeting ZE3. Thus, the RIC platform can be more generally applied to a wider variety of antigens.
Databáze: OpenAIRE
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