The Safe Baculovirus-Based PrM/E DNA Vaccine Protected Fetuses against Zika Virus in A129 Mice

Abstract

The Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family of enveloped RNA viruses. The correlation between viral infection and fetal microcephaly was revealed in 2015, yet we still lack a vaccine against ZIKV. Here, we present a genetic vaccine that delivers the premembrane (prM) and envelope (E) genes of ZIKV using a recombinant baculovirus vector that expresses a human endogenous retrovirus (HERV) envelope on its surface to enhance gene delivery. We observed that baculoviruses with HERV envelopes (AcHERV) exhibited specifically higher gene transfer efficiency in human cells compared to the wild-type baculovirus vector. Using the AcHERV baculovirus vector, we constructed a recombinant baculovirus vaccine encoding ZIKV prM/E genes (AcHERV-ZIKV), which are major targets of neutralizing antibodies. Mice immunized twice with AcHERV-ZIKV exhibited high levels of IgG, neutralizing antibodies, and IFN-γ. In challenge tests in IFN knock-out mice (A129), AcHERV-ZIKV showed complete protection in both challenge and pregnancy tests. These results suggest that AcHERV-ZIKV could be a potential vaccine candidate for human application.

Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice

“…We had previously developed MERS-CoV, SARS-CoV2, and Zika virus vaccines using a baculovirus-based DNA vaccine (AcHERV) system (9, 12). Here, we demonstrated that AcHERV-COVID19D could be a potential SARS-CoV2 vaccine against pathogenic Delta and Omicron variants.…”

Human endogenous retroviruses in viral disease and therapy

“…Recently, the AcHERV system has been applied to develop a vaccine against Zika virus (AcHERV‐ZIKV), and AcHERV‐ZIKV induced the expression of high levels of IgG, neutralizing antibodies and IFN‐γ in mice. Moreover, AcHERV‐ZIKV conferred complete protection to IFN‐knockout (A129) female mice, pregnant mice and fetal mice challenged with ZIKV 76 . In addition to vaccine vectors, HERVs have also been used as vaccine adjuvants.…”

“…Moreover, AcHERV-ZIKV conferred complete protection to IFN-knockout (A129) female mice, pregnant mice and fetal mice challenged with ZIKV. 76 In addition to vaccine vectors, HERVs have also been used as vaccine adjuvants. Choi et al reported that female mice immunized with an inactivated influenza vaccine together with a murine granulocyte-macrophage colony-stimulating factor (GmCSF) gene delivered by the AcHERV system showed stronger humoural and cellular immune responses than mice immunized with the inactivated vaccine alone.Influenza-GmCSF-vaccinated mice were fully protected from lethal influenza virus challenge.…”

Vectored-Vaccine Platforms Enabled Rapid Development of Safe and Effective Vaccines in Response to COVID-19 Pandemic Situation

“…The focus of the global research and development efforts on designing, developing, and delivering safe and effective COVID-19 vaccine candidates should not undermine the continuing efforts to develop vaccines against other infectious diseases. Choi et al [ 7 ] explore the use of a recombinant baculovirus-vectored vaccine against Zika virus infection (ZIKV), demonstrating immunogenicity and protection in mice studies. The recombinant baculovirus vector is pseudo-typed with a human endogenous retrovirus envelope to enhance gene delivery of the premembrane and envelope genes of ZIKV, and the authors demonstrate immunogenicity and protection in mice studies.…”