Incorporation of NS1 and prM/M are important to confer effective protection of adenovirus-vectored Zika virus vaccine carrying E protein

Abstract

Current design of Zika virus (ZIKV) vaccine mainly considered envelope (E) as the major target antigen. Non-structural protein NS1 was seldom considered. Herein, we generated three adenovirus-vectored vaccines carrying E (Ad2-E), or premembrane/membrane (prM/M) with E (Ad2-prME), or NS1 in addition to prM/M with E (Ad2-prME-NS1). Ad2-prME induced higher neutralizing antibody response to ZIKV than Ad2-E, suggesting prM/M is important for the folding of immunogenic E. Most intriguingly, Ad2-prME-NS1 elicited the best viral inhibition when the immune sera were added to ZIKV-infected cells. In ZIKV-challenged neonatal mice born to maternally immunized dams, Ad2-prME-NS1 conferred the best protection in preventing weight loss, neurological disorders, and viral replication. Ad2-prME also conferred significant protection but was less effective than Ad2-prME-NS1, whereas Ad2-E only alleviated neurological symptoms but did not inhibit viral replication. Our study suggested that NS1 should be considered in the design of ZIKV vaccine in addition to prM/M and E.

Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice

“…This is consistent with previous reports that the incorporation of NS1 into E-protein-based vaccine enhanced its protective efficacy against experimental DENV and ZIKV infections. 19 , 50 , 51 In these models, the specific relationships between immune responses and the NS1 protein in the overall protection are yet to be understood. We reason that there are several ways in which NS1 specific immune responses play a beneficial role.…”

Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model

“…As many candidate flavivirus vaccines omit the NS1 component 40 , it is possible that antibodies targeting the NS1 are overlooked in the protective immune response to ZIKV infection in humans. Of note, a recent study highlights the importance of incorporating NS1 in a multivalent vaccine against ZIKV 41 . Though Zika virus has one serotype with regards to a neutralizing response 42 , less is known about whether non-neutralizing antibodies against NS1 are able to target multiple strains of the virus.…”

Recent Advances in Zika Virus Vaccines

“…This prMEΔTM region in a chimpanzee adenoviral vector (ChAdOx1) provided better neutralizing response than the full length prME, suggesting that modification of antigen membrane anchor can enhance immunogenicity. Liu et al [ 69 ] recently included the NS1 gene of ZIKV along with prME (isolate 1_0080_PF, Accession # KX447521) in an Adenovirus serotype 2 vector system to generate Ad2-prME-NS1 vector. The Ad2-prME-NS1 vector resulted in both Env as well as NS1 specific antibodies, and protected pups born to immunized dams against Zika induced pathology.…”