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.

Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

“…The intact S glycoprotein rather than the shorter S or RBD proteins was shown to be the most effective antigen eliciting protective immunity against SARS-CoV-2 infection in DNA vaccines and Ad26 vectored vaccines ( 12,13,26 ). The vectors Sad23L and Ad49L originated from simian adenovirus type 23 and human adenovirus type 49, respectively ( 22, 23 ), are novel adenoviral vector. Comparing Ad5-vectored COVID-19, ChAdox1 nCoV-19 and Ad26.COV2.S vaccines ( 8-12,14,21 ), three attractive aspects emphasized in this study are highlighted below.…”

“…According to the description of Sad23L vector (SAdV23, GenBank: AY530877.1) ( 22, 23 ), the replication defective adenoviral vector Ad49L was constructed by deleting the E1 and E3 regions of the full-length human adenovirus serotype 49 genome (HAdV49, GenBank: DQ393829.1). The E4 region open reading frame 6 (orf6) was replaced by the corresponding element of human adenovirus type 5 (Ad5) in order to improve virus propagating efficiency.…”

“…The vaccine strains were serially passaged for stability by 12 generations when the full cytopathic effect appeared. Virus purification was performed by cesium chloride density gradient centrifugation as previously described ( 23 ).…”

“…Genomic DNA was extracted from homogenized tissue of adenovirus vectored vaccine inoculated mice by High Pure Viral Nucleic Acid Kit (Roche). DNA fragments of Sad23L and Ad49L vectors were amplified by nested PCR with primers specific to adenoviral hexon sequences (Table S4) ( 23 ).…”

“…In this study, two novel simian adenovirus type 23 (SAdV23) and human adenovirus type 49 (HAdV49) derived vectors (Sad23L and Ad49L) were used for developing the COVID-19 vaccines carrying the full-length S gene of SARS-CoV-2 ( 22, 23 ) designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. These two adenovirus vectored COVID-19 vaccines presented high infectious titers and low frequencies of pre-existing immunity in humans.…”