Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. Here, we evaluated the utility of ChAdOx1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for MERS-CoV vaccine development. Using a transgenic lethal BALB/c MERS-CoV mouse model we showed that single dose intranasal or intramuscular immunisation with ChAdOx1 MERS, encoding full-length MERS-CoV Spike glycoprotein, is highly immunogenic and confers protection against lethal viral challenge. Immunogenicity and efficacy were comparable between immunisation routes. Together these data provide support for further evaluation of ChAdOx1 MERS vaccine in humans and dromedary camels, the animal reservoir of infection.

Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China

“…Apart from the inactive whole virus particle [30], live attenuated virus with gene deletion [31] , four more vaccines which mainly contain S protein were studied. These include a virus-like particle which incorporated S protein into hepatitis virus or influenza virus protein [32,33]; virus vectors, such as modified vaccinia virus Ankara (MVA) or Adenovirus carrying S protein [34,35]; S protein subunit vaccine, like RBD-based protein [29,36]; and DNA vaccine which encodes the full length or part of the S protein gene [37,38]. Most of them have been tested in mouse models and showed the ability to elicit neutralizing antibodies.…”

Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice

“…In this study, potentially protective humoral and cellular immune responses were elicited in mice by immunization using a recombinant adenoviral-based vaccine encoding the S1 subunit of the MERS-CoV spike gene. Several studies have been published that constructed similar vaccines against MERS-CoV and tested their ability to induce production of neutralizing antibodies and other immune system components [13,14,17,[19][20][21][22][23]. The results of these studies were encouraging and showed that -12], and IL-4) in vitro.…”

“…There have been several attempts to develop a protective vaccine against MERS-CoV [12][13][14][15][16][17][18][19][20][21][22][23]. Researchers around the world are focused on the spike protein as the main target for vaccine development against MERS-CoV.…”

“…Recombinant adenoviral vector vaccines are one of the most effective vaccines and showed interesting results during SARS-CoV outbreaks [12,26,27]. Since 2013, several studies were published, in which different viral vectors (e.g., adenoviruses and vaccinia virus) were used to develop recombinant vaccine candidates based on full spike gene or part of it and tested their ability to produce protective immunity against MERS-CoV infection [13][14][15][16][17][18][19][20][21][22][23]. However, further investigations are needed on these suggested vaccines including testing their ability to elicit neutralizing antibodies in different animal models, stimulation of both innate and adaptive immune responses and their corresponding cytokine and chemokine profiles, distribution within the host, and their safety and duration profiles.…”

Vaccine platforms for the prevention of Lassa fever

“…Application of the ChAdOx1 platform to a diverse range of emerging pathogens is supported by multiple studies demonstrating that a single dose of ChAdOx1-vectored vaccine fully protected inbred BALB/c mice, sheep, goats, and cattle from lethal Rift Valley fever, protected 100% of transgenic human dipeptidyl peptidase-4 mice from lethal Middle East respiratory syndrome, and offered inbred BALB/c mice sterilising protection from Zika virus infection [107][108][109][110]. Each of these vaccine candidates has potently induced antigen-specific T-cell responses and high titre neutralising antibodies [107][108][109][110][111].…”