ChAdOx1 is an

adenoviral Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from thei ...

vector for vaccines that was developed by the Jenner Institute,

University of Oxford The University of Oxford is a collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the world's second-oldest university in contin ...

. The

vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...

is a chimpanzee adenovirus modified to avoid its replication. Adenoviruses are effective vectors for inducing and boosting

cellular immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines ...

to encoded recombinant

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s. However, the widespread

seroprevalence Seroprevalence is the number of persons in a population who test positive for a specific disease based on serology (blood serum) specimens; often presented as a percent of the total specimens tested or as a proportion per 100,000 persons tested. As ...

of neutralizing antibodies to common human adenovirus

serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the e ...

s limits their use. Simian adenoviruses do not suffer from the same disadvantages. Therefore, investigators have tested new vaccines using the chimp adenovirus ChAdOx1 as a vector. For example, a vaccine for

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...

infection was designed using the vector expressing influenza antigens,

nucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating inte ...

(NP), and

matrix protein Viral matrix proteins are structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane. They are found in many enveloped virus ...

1 (M1), creating a vaccine candidate named ChAdOx1 NP+M1. __TOC__

Virology

ChAdOx1 has been derived from a chimpanzee adenovirus (ChAd) serotype Y25 engineered by

λ red recombination ''Enterobacteria phage λ'' (lambda phage, coliphage λ, officially ''Escherichia virus Lambda'') is a bacterial virus, or bacteriophage, that infects the bacterial species '' Escherichia coli'' (''E. coli''). It was discovered by Esther Lede ...

to exchange the native E4

orf ORF or Orf may refer to: * Norfolk International Airport, IATA airport code ORF * Observer Research Foundation, an Indian research institute * One Race Films, a film production company founded by Vin Diesel * Open reading frame, a portion of t ...

4, orf6 and orf6/7 genes for those from human adenovirus HAdV-C5. Serotype Y25 belongs to the species ''

Human mastadenovirus E Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultur ...

'' of genus ''

Mastadenovirus ''Mastadenovirus'' is a genus of viruses in the family ''Adenoviridae''. Humans and other mammals serve as natural hosts. There are 51 species in this genus. The genus as a whole includes many very common causes of human infection, estimated to ...

''.

Clinical trials

It has been demonstrated that the adenoviridae vector ChAdOx1 can be used to make vaccinations that are protective against

Middle East Respiratory Syndrome Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by '' Middle East respiratory syndrome–related coronavirus'' (MERS-CoV). Symptoms may range from none, to mild, to severe. Typical symptoms include fever, cough, ...

(MERS) in mice and able to induce immune response against MERS in humans. The vector was also used to create a vaccine against

Nipah NIPA, Nipa or nipah may refer to: * Shamim Ara Nipa, Bangladeshi dancer and choreographer * Nipa hut, a type of stilt house indigenous to the cultures of the Philippines * Nipah virus, a Henipavirus NIPA * National Income and Product Accoun ...

which was effective in hamsters (but never proven in humans), in addition to a potential vaccine for Rift Valley Fever that was protective in sheep, goats, and cattle (but not proven in humans). The adenovirus expressing the antigen 85A (ChAdOx1 85A), is used as vector for a tuberculosis vaccine candidate. In 2017, the ChAdOx1 vector was used in a trial for a vaccine candidate against human

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or deat ...

infection. The researchers studied two candidate vaccines ChAdOx1 LS2 along with MVA LS2. The former, encoding a malaria liver-stage dual antigen LS2 (LSA1 and LSAP2) fused with the transmembrane domain from shark invariant chain. And the latter, a

Modified Vaccinia Ankara Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine (called MVA-BN, brand names: Imvanex in the EU, Imvamune in Canada, and Jynneos in the US) against smallpox and monkeypox, ...

(MVA) vector encoding the LS2 fused to the C-terminal end of the leader sequence of tPA. The trial reached the phase I/IIa. There are also investigation lines that use the vector for vaccines against the

Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family '' Flaviviridae''. It is spread by daytime-active '' Aedes'' mosquitoes, such as ''A. aegypti'' and ''A. albopictus''. Its name comes from the Ziika Forest of Uganda, wh ...

(ChAdOx1 ZIKV) and the

Chikungunya Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a ras ...

virus (ChAdOx1 sCHIKV). The ChAdOx1 vector has been used as a platform for a vaccine against

coronavirus disease Coronavirus diseases are caused by viruses in the coronavirus subfamily, a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, the group of viruses cause respiratory tract infections that can range fro ...

since the beginning of the

COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identified ...

Sarah Gilbert Dame Sarah Catherine Gilbert (born April 1962) is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emerging ...

leads the work on this vaccine candidate alongside Andrew Pollard, Teresa Lambe, Sandy Douglas, Catherine Green and

Adrian Hill Adrian Keith Graham Hill (24 March 1895 – 1977) was a British artist, writer, art therapist, educator and broadcaster. Hill served with the Honourable Artillery Company during World War I and was the first artist commissioned by the Imperi ...

. The

COVID-19 vaccine A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID19). Prior to the COVID19 pandemic, an est ...

, known now as ChAdOx1 nCoV-19 or AZD1222, makes use of this vector, which stimulates an immune response against the coronavirus

spike protein In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers o ...

. Animal studies began in March 2020, and recruitment of 510 human participants for a phase I/II trial began on 27 March, and the results were presented in October. On 30 December 2020, the vaccine was approved for use in the UK's vaccination programme.

References

{{Use British English, date=December 2020 Adenoviridae Clinical trials COVID-19 vaccines