A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection

Abstract

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×10 ⁸ PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 10 ^4.07 E-specific and 10 ^3.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/10 ⁶ cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (10 ⁵ PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<10 ³ copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >10 ^3.66) and T-cell response (>726 SFCs/10 ⁶ PBMCs) were acquired 1–2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (10 ^5.73 copies/ml) ( P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.

Author summary

Zika virus (ZIKV) is a member of the Flaviviridae family) and causes severe neurologic diseases. The development of safe and effective vaccine is urgent need. In this study, we constructed a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E). By vaccinating the common marmosets with prime immunization of vaccine, and upon challenge with a high dose of ZIKV to the vaccinated marmosets, the immune response and protective efficacy of vaccine were extensively evaluated. The data suggested that Sad23L-prM-E vaccine could protect marmosets against a high dose of ZIKV challenge, which provided a promising vaccine for preventing ZIKV infection in humans.