The vaccinia virus based Sementis Copenhagen Vector vaccine against Zika and chikungunya is immunogenic in non-human primates

Abstract

The Sementis Copenhagen Vector (SCV) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. Indian rhesus macaques (Macaca mulatta) were vaccinated with a multi-pathogen recombinant SCV vaccine encoding the structural polyproteins of both Zika virus (ZIKV) and chikungunya virus (CHIKV). After one vaccination, neutralising antibody responses to ZIKV and four strains of CHIKV, representative of distinct viral genotypes, were generated. A second vaccination resulted in significant boosting of neutralising antibody responses to ZIKV and CHIKV. Following challenge with ZIKV, SCV-ZIKA/CHIK-vaccinated animals showed significant reductions in viremias compared with animals that had received a control SCV vaccine. Two SCV vaccinations also generated neutralising and IgG ELISA antibody responses to vaccinia virus. These results demonstrate effective induction of immunity in non-human primates by a recombinant SCV vaccine and illustrates the utility of SCV as a multi-disease vaccine platform capable of delivering multiple large immunogens.

A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

“…A potential issue for ZIKV vaccines is that they (if perhaps poorly designed) might induce ADE of DENV infection. Using a previously established female IFNAR −/− mouse model of DENV-D220 ADE [ 19 ], the ability of BinJ/ZIKA-prME vaccination to induce DENV ADE was assessed. IFNAR −/− mice were vaccinated with 2 µg or 20 µg of BinJ/ZIKA-prME, or were mock vaccinated with PBS; mice were then infected with DENV-D220 ( Figure 3 a).…”

“…DENV viremia in the 20 µg BinJ/ZIKA-prME was slightly lower than the PBS controls, although this reached significance only on day 3 ( Figure 3 b). In this model ADE manifests as increased weight loss [ 19 ]; however, weight loss in BinJ/ZIKA-prME vaccinated mice was actually significantly reduced when compared with PBS controls ( Figure 3 c). These results are consistent with the serological cross-reactivity between ZIKV and DENV antibodies [ 41 ], but suggests that for BinJ/ZIKA-prME vaccination, this manifests as mild cross-protection against viremia rather than ADE.…”

“…ADE may be associated with reduced type I IFN responses [ 52 , 53 , 54 , 55 ], a manifestation potentially difficult to discern in IFNAR −/− mice; nevertheless, severe DENV pathology and ADE has been independently demonstrated in type I IFN response-deficient mice [ 56 , 57 ]. Severe DENV disease is also usually associated with vascular leakage and/or hemorrhage [ 58 ], whereas only weight loss was demonstrated in our model [ 19 ]. When clinical correlates of DENV ADE by anti-ZIKV antibodies are better characterized [ 24 ], it may become easier to design appropriate preclinical systems that can provide more definitive assurances.…”

“…A DENV-D220 female IFNAR −/− ADE mouse model has been described previously, with ADE (mediated by prior injection of an anti-flavivirus E specific antibody) manifesting as significantly increased weight loss and mortality post DENV infection [ 19 ]. Female IFNAR −/− mice (4 to 24 weeks old, n = 6 per group with a similar age distribution in each group) were anaesthetized and vaccinated once with either 2 µg BinJ/ZIKA-prME, 20 µg BinJ/ZIKA-prME, or PBS (in 50 µL) injected into each quadriceps femoris muscle.…”

Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models

“…One immunization with SCV-ZIKA/CHIK was previously shown to protect against viremia and disease after CHIKV challenge in an adult wild-type mouse model [ 16 , 28 ]. SCV-ZIKA/CHIK also induced neutralizing antibodies to CHIKV in non-human primates [ 29 ].…”