Immunogenicity was examined following challenge with EBOV (strain Mayinga). induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely Aspartame dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as Aspartame high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine. Author Summary Ebola virus (EBOV) has been associated with outbreaks in human and nonhuman primate populations since 1976. With a fatality rate approaching 90%, EBOV is one of the most lethal infectious diseases in humans. The increased frequency of EBOV outbreaks along with its potential to be used as a bioterrorism agent has dramatically strengthened filovirus vaccine research and development. While there are currently no approved vaccines or post exposure treatments available for human use, several vaccine candidates have shown to protect nonhuman primates from lethal EBOV challenge. Our primary focus is to develop vaccine candidates to protect humans and endangered wildlife species at risk of infection in Africa. Here, we evaluated the efficacy and immunogenicity of our dual vaccines against EBOV and rabies virus (RABV) in rhesus Aspartame macaques. Our live replication-competent vaccine provided 100% protection following EBOV challenge while the replication-deficient and inactivated candidates provided 50% protection. Interestingly, protection is dependent on the quality of the antibodies rather than the quantity. All three RABV-based EBOV vaccines did induce antibody levels necessary for protection from RABV infection. These results encourage the further development of these novel dual vaccines directed against two of the most lethal viral diseases. Introduction Several members of the genus and genus, Aspartame Family recently concluded that EBOV-specific CD8+ T cells and not Rabbit polyclonal to ZDHHC5 humoral immunity mediated protection from EBOV infection upon adenovirus/EBOV-GP immunization [13]. Collectively, these studies suggest that immune parameters that correlate with and/or confer protection may be multi-factorial and vary by vaccination platform. However, we also need to consider that there are likely different requirements for the induction of anti-EBOV immunity and the recall response after exposure to the pathogen. It is not likely that long-lived immunity can be achieved without T-helper cells. In the case of GP-specific antibodies it needs to be shown that they are maintained over time or CD4+ T helper cells will be required to mount fast responses after infection. A filovirus vaccine would be directed for use in humans at risk of infection in Africa as well as for laboratory workers, healthcare providers, first responders, soldiers, or travelers. Furthermore, EBOV vaccines could be utilized in endangered wildlife species such as gorillas and chimpanzees in Central Africa where they are at risk of lethal EBOV disease. Epidemiologic studies have indicated that EBOV outbreaks have resulted in numerous deaths of these animals in Gabon and the Democratic Republic of Congo, hindering conservation efforts to protect these populations [14]C[16]. A vaccine to protect these at risk NHPs would have a second critical benefit to humans. As EBOV is a zoonotic disease with documented human outbreaks, which can arise from contact with diseased NHPs [17], prevention of disease in these animals might reduce the frequency of EBOV Aspartame transmission into humans resulting in reduced frequency of outbreaks. Our goal is to identify a vaccine platform for EBOV and other filoviruses of public health importance that would (a) produce promising candidates for use in both humans and endangered wildlife species and (b) yield multiple vaccine candidates increasing the likelihood that an optimal balance between reactogenicity and immunogenicity might be achieved..
