Homologous prime-boost with Zika virus envelope protein and poly (I:C) induces robust specific humoral and cellular immune responses

被引:17
作者
Amaral, Marcelo Pires [1 ]
Apostolico, Juliana de Souza [1 ,2 ]
Tomita, Nadia [1 ]
Coirada, Fernanda Caroline [1 ]
Santos Lunardelli, Victoria Alves [1 ,2 ]
Fernandes, Edgar Ruz [1 ]
Santos Souza, Higo Fernando [3 ]
Astray, Renato Mancini [4 ]
Boscardin, Silvia Beatriz [2 ,3 ]
Rosa, Daniela Santoro [1 ,2 ]
机构
[1] Fed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
[2] INCT, Inst Invest Immunol 3, Sao Paulo, Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, Brazil
[4] Butantan Inst, Viral Immunol Lab, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
Subunit vaccine; DNA vaccine; Prime-boost; Adjuvant; Envelope; Zika virus; DNA VACCINE; INFECTION; CELLS;
D O I
10.1016/j.vaccine.2020.03.037
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The recent outbreaks of Zika virus (ZIKV) infection and the potential association with Guillain-Barre syndrome in adults and with congenital abnormalities have highlighted the urgency for an effective vaccine. The ZIKV Envelope glycoprotein (E-ZIKV) is the most abundant protein on the virus surface, and has been evaluated together with the pre-membrane protein (prM) of the viral coat as a vaccine candidate in clinical trials. In this study, we performed a head-to-head comparison of the immune response induced by different E-ZIKV-based vaccine candidates in mice. We compared different platforms (DNA, recombinant protein), adjuvants (poly (I:C), CpG ODN 1826) and immunization strategies (homologous, heterologous). The hierarchy of adjuvant potency showed that poly (I:C) was a superior adjuvant than CpG ODN. While poly (I:C) assisted immunization reached a plateau in antibody titers after two doses, the CpG ODN group required an extra immunization dose. Besides, the administration of poly (I:C) induced higher E-ZIKV-specific cellular immune responses than CpG ODN. We also show that immunization with homologous prime-boost EZIKV protein + poly (I:C) regimen induced a more robust humoral response than homologous DNA (pVAX-E-ZIKV) or heterologous regimens (DNA/protein or protein/DNA). A detailed analysis of cellular immune responses revealed that homologous (E-ZIKV + poly (I:C)) and heterologous (pVAX-E-ZIKV/E-ZIKV + poly (I:C)) prime-boost regimens induced the highest magnitude of IFN-gamma secreting cells and cytokine-producing CD4(+) T cells. Overall, our data demonstrate that homologous E-ZIKV + poly (I:C) prime-boost immunization is sufficient to induce more robust specific-E-ZIKV humoral and cellular immune responses than the other strategies that contemplate homologous DNA (pVAX-E-ZIKV) or heterologous (pVAX-E-ZIKV/E-ZIKV + poly (I:C), and vice-versa) immunizations. (C) 2020 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3653 / 3664
页数:12
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