Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus

Abstract

Zika virus (ZIKV) is a significant public health concern due to the pathogen's ability to be transmitted by either mosquito bite or sexual transmission, allowing spread to occur throughout the world. The potential consequences of ZIKV infection to human health, specifically neonates, necessitates the development of a safe and effective Zika virus vaccine. Here, we developed an intranasal Zika vaccine based upon the replication-deficient human adenovirus serotype 5 (hAd5) expressing ZIKV pre-membrane and envelope protein (hAd5-ZKV). The hAd5-ZKV vaccine is able to induce both cell-mediated and humoral immune responses to ZIKV epitopes. Importantly, this vaccine generated CD8 + T cells specific for a dominant ZIKV T cell epitope and is shown to be protective against a ZIKV challenge by using a pre-clinical model of ZIKV disease. We also demonstrate that the vaccine expresses pre-membrane and envelope protein in a confirmation recognized by ZIKV experienced individuals. Our studies demonstrate that this adenovirus-based vaccine expressing ZIKV proteins is immunogenic and protective in mice, and it encodes ZIKV proteins in a conformation recognized by the human antibody repertoire.The development of a ZIKV vaccine is urgent due to the speed of ZIKV spread in susceptible populations, as well as the range of diseases caused by infection [5]. According to the World Health Organization (WHO), a majority of individuals who are infected with ZIKV are asymptomatic, but those with a mild clinical form of the disease report symptoms including fever, rash, conjunctivitis, and muscle and joint pain, all of which typically last less than a week. While these symptoms are rarely debilitating, complications of Zika virus disease can include Guillain-Barré syndrome. Zika-induced microcephaly and congenital abnormalities are generally classified as congenital Zika syndrome (CZS), which is also a potential complication in the developing fetuses of pregnant women [4,6-10]. These risks, combined with the explosive outbreaks that occurred at Yap Island in 2007 [11], French Polynesia in 2013 [12], and Brazil in 2015-16 [13], underscore the need to control the spread of ZIKV. However, there are no current FDA-approved vaccines available to control infection.Harnessing the power of both arms of the adaptive immune response improves vaccine potency and efficacy while reducing opportunities of viral escape. Current data from both naturally acquired human infection and mouse models of ZIKV disease indicate that protection from disease is multi-faceted (reviewed in [14][15][16][17][18]). Both small and large animal models of ZIKV infection have demonstrated that the Zika-specific CD8 + and CD4 + T cell response is necessary and sufficient to protect against a lethal ZIKV challenge [19][20][21][22]. As has been demonstrated previously for multiple flavivirus infections [23-25], ZIKV-specific polyclonal and monoclonal neutralizing antibody responses can protect mice and nonhuman primates from mortality and severe disease. There is also a role fo...

Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic

“…Importantly, the broad tissue tropism of Ads and their ability to drive strong expression of the target antigen helps position them as one of the most immunogenic viral vectors [35][36][37] . This capacity to elicit strong immune responses has been exploited to develop vaccine candidates for infectious diseases such as Acquired immunodeficiency syndrome (AIDS), Ebola virus disease, Zika virus disease, Malaria and Tuberculosis [38][39][40][41][42] and for cancer immunotherapies 43 . Among these candidates, a recombinant Ad serotype 26 vaccine expressing a Zaire Ebola virus glycoprotein has recently demonstrated the ability to protect humans against Ebola virus disease 44 .…”

The combined vaccination protocol of DNA/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses

“…However, a significant increase in the magnitude of adaptive and memory ZIKV-specific CD4 + T cell responses was achieved when a DNA-ZIKV/MVA-ZIKV heterologous prime/boost regimen was applied. On the other hand, recent studies have confirmed the importance of CD8 + T cells in ZIKV infection and in vaccine-induced protection [ 51 , 53 , 54 ]. Furthermore, in a ZIKV infection model it has been described that CD8 + T cells are capable of local viral control if they arrive in the brain early after viral invasion, demonstrating the benefits of considering this subset when designing vaccines against ZIKV virus [ 38 ].…”

Current Progress in the Development of Zika Virus Vaccines

“…An intranasal Zika vaccine based on the replication-deficient hAd5 expressing ZIKV prM and E proteins recognized by the human antibody repertoire was able to induce both cell-mediated and humoral immune responses, which conferred protection against ZIKV challenge as demonstrated in a preclinical model of ZIKV infection [41]. Two novel hAd5vector vaccines expressing ZIKV prM-E (Ad5-Sig-prM-Env) and E (Ad5-Env) proteins were constructed and evaluated in multiple non-lethal and lethal animal models using epidemic ZIKV strains [42].…”