Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine.

Yusen Zhou,Lanying Du,Chuanlai Shen,Xiaolu Zhang,Xinyi Wang,Wanbo Tai

doi:10.3390/vaccines7040161

Yusen Zhou, Lanying Du + Show 4 more

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https://doi.org/10.3390/vaccines7040161

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Abstract

Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.

Highlights

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated from a rhesus macaque in Uganda in 1947 [1]
This study has identified the combination of aluminum salts (Alum) and Monophosphoryl lipid A (MPL) as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses
Our results show that a more balanced (Th1/Th2) immune response is generated and that the immunogenicity and the ability to protect against ZIKV infection are significantly enhanced when both Alum and MPL are used in the same vaccine formulation

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated from a rhesus macaque in Uganda in 1947 [1]. Some adults infected with ZIKV present with Guillain–Barré syndrome (GBS), a disorder of the nervous system that results in muscle weakness and/or paralysis [2,3]. Infection during pregnancy may cause congenital Zika syndrome (CZS), which is associated. Vaccines 2019, 7, 161 with microcephaly, fetal demise, and other congenital disorders [4,5,6]. The E protein has important roles in infection and pathogenesis, is involved in virus binding to target cells and membrane fusion, and serves as an important vaccine target [7,8]. The E protein is a transmembrane protein and consists of three domains termed I, II, and III (DI–DIII), a fusion loop (FL), and a stalk region (S) [8].

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