Non-Replicating Viral Vector (nRVV) Vaccines

What is an nRVV vaccine?

Non-replicating viral vector vaccines use what’s called an adenovirus (which causes the common cold) in order to transfer the COVID protein into a human subject, in order to trigger a response from the immune-system. The COVID protein is either left in a weakened or killed state, thus restricting the protein from altering the cell negatively, as the live virus does. The adenovirus, which is either human or simian-derived (usually from chimpanzees), is genetically-modified to not be able to replicate.

The protein used to trigger the immuno-response is called the SARS-CoV-2 Spike Protein. This is what allows the coronavirus to successfully invade the cells, therefore filling the same role within the adenovirus. Much like aforementioned Messenger RNA vaccines, there are currently no vaccines that use this strategy of disease-prevention for humans commercially available as of yet.

Candidate is now named Convidicea. Multiple trials currently in various stages of progress.

A Stage 1 trial in China of 108 participants (ages 18-60)(split into 3 dose-size groups). Another Stage 1 trial in China evaluating intramuscular and mucosal vaccination (6 groups of 24)(double-dose). 1 Stage 1/2 trial in Canada of 696 healthy participants (ages 18-55, and ages 65-85)(randomised, observerblind, dose-dependant). A Stage 2 trial in China of 508 participants (ages 18+) (randomised, observer-blind, placebo-controlled). A Stage 2b trial in China evaluating immunogenicity and safety in 481 participants (ages 6+)(randomised, double-blind, placebo-controlled). 1 Stage 3 trial in Russia of 500 healthy participants (across multiple sites). 1 Stage 3 trial of 40,000 participants on an international scale, including Mexico, Pakistan, and Saudi Arabia.

Single dose protected against respiratory infection from SARS-CoV-2 in ferrets.

Stage 1 trial results showed a humoral and immunogenic response.

Results also displayed adverse reactions such as fevers (46%), and fatigue (44%), etc, in 83% of participants with low-mid dosage, and 75% of participants given a higher dosage. Stage 2 trials showed significant neutralising antibody responses at all dose-levels for all participants.

Notes & Status

Adenovirus used is derived from a human. On June 25th, China’s Military Commission approved the vaccine for military use for a 1 year period. A vaccine developed by CanSino has been submitted to the Mexican health regulator Cofepris for review, but it has not been clarified whether this vaccine is Convidicea.

CanSino Biologics Official Report Data The tech for Janssen’s candidate was built on development for Ebola vaccine, and vaccine candidates for Zika and HIV. Candidate is currently only going by the name of JNJ-78436735.

Currently 1 Stage 1/2a* study is underway

Study sites are planned between the UK and Belgium (randomised, double-blind, and placebo-controlled) (1045 - healthy adults aged 18-55 yrs old, and 65+)

September 23 - Stage 3 ENSEMBLE trial announced, soon followed by a 2nd Stage 3 trial. Both are still ongoing.

60,000 adults, including those over 60, and those with pre-existing underlying health conditions Paused on October 12 due to unexplained illness in one participant, but ultimately resumed on October 23 as per recommendation from the Independent Data Safety and Monitoring Board. As of Nov. 4, another Stage 3 trial began, named ENSEMBLE 2, consisting of 30,000 healthy adult participants, and has since been running alongside the first trial.

September 25 - Preliminary Stage 1/2a results were posted.

Showed that a single dose of the candidate exhibited immunogenicity and ‘a good safety profile.’ As well as complete or near-complete protection for animal subjects, in this case, hamsters and macaques

Internal & External Funding

JNJ-78436735 is funded by Janssen, BARDA, NIAID and Operation Warp Speed. In partnership with BARDA, Janssen has committed to investing more than $1 billion in vaccine research and development.

Notes & Status

The adenovirus used for JNJ-78436735 is a human-derivative. Janssen said it plans to begin testing its vaccine in adolescents “as soon as possible.” Australia’s Therapeutic Goods Administration (TGA) has granted Provisional Determination to the candidate, to allow for a faster approval in the country. Janssen’s vaccine candidate has also started a rolling review with the European Medicines Agency (EMA).

Johnson & Johnson Official Report Data

Non-Replicating Viral Vector (nRVV) Vaccines

s c adenovirus r v s 2 -

The adenovirus is used as a trojan horse to allow the SARS-Cov-2 protein into the cell to produce an immunogenic response.

adenovirus

cell wall

CanSino Biologics Official Report Data Johnson & Johnson Official Report Data

Non-Replicating Viral Vector (nRVV) Vaccines

Candidate is named CoviShield, taken twice 4-12 weeks apart.

Currently 4 large-scale trials are ongoing.

Stage 3 trial of 40,000 healthy participants (doubledose, placebo-controlled). Stage2/3 trial of 12,390 healthy participants ongoing in the UK split into 12 groups depenant on age (18-85 altogether, group 12 consists of HIV positive adults ages 18-55)(randomised, dose-dependant, and placebo-controlled). Stage 1/2 trial of 1,090 healthy participants (18-55) (single-blinded, multi-center study). Stage 1/2 trial of healthy participants in South Africa is underway, and finished recruitment.

A small-scale trial is also currently underway to test an inhaled vaccine (30 participants).

Strong immune response in all age groups.

Average efficacy rate of 70% over all dose-levels. 62.1% efficacy for those who received 2 full doses, and 90% efficacy for those who received first only a half-dose, and then a full dose. Similar immunogenicity was observed in all age groups, but appeared better-tolerated in older adults. Early results showed a ‘good safety profile,’ with most participants showing a response after one dose, and all participants after both.

Only minor side-effects of headache and fatigue were exhibited in preliminary results.

Trials were paused momentarily in September due to an adverse reaction in one participant that resulted in death. Production resumed again early in October after approval was given.

Regulatory Actions

On 29 December, MHRA authorized COVID-19 Vaccine AstraZeneca for use in the United Kingdom. It has also been authorized for use in India, Argentina, Dominican Republic, El Salvador, Mexico and Morocco. EMA’s human medicines committee (CHMP) has started a rolling review of the vaccine to reduce the amount of time before a decision is made on safety and effectiveness, as has Health Canada. In Australia, TGA granted AstraZeneca’s vaccine provisional determination, the first step in the process for approval.

Internal & External Funding

The AstraZeneca trials are funded in part by BARDA and OWS. The $1.2 billion paid by OWS for 300 million doses of the vaccine in the US also funded research and clinical testing.

Notes & Status

The adenovirus used for this candidate is derived from a chimpanzee.

AstraZeneca / Oxford University Official Report Data

First approved vaccine.

Already approved by the Health Ministry of Russian Federation as the first vaccine - no trial data published up to this point. The approval has drawn criticism from the medical community.

Stage 1/2 trials completed

Recruited about 38 participants each to receive the vaccine candidate. Results showed a good safety profile and ‘induced strong humoral and cellular immune response’ in the participants.

Stage 2 and 3 trials being carried out between Russia, Belarus, and United Arab Emirates.

1 small Stage 2 trial is taking place in Russia (110 participants aged 60+). 1 Stage 3 trial taking place in Russia (40,000 participants).

2 strains of adenovirus (named ‘GAM-Covid-Vac,’ and ‘GAMCovid-Vac Lyo’)

2 full doses, with 21 days in-between. Was announced to have a ‘good safety profile’ and ‘strong cellular immune response,’ along with a 92% efficacy rate. However, this set of results only used 20 participants, so the results at this point were unconvincing.

Dec 14 - Interim trial results were announced

91.4% efficacy rate was shown based on 22,714 participants, although these results have not yet been peer-reviewed.

Regulatory Actions

The Health Ministry of the Russian Federation approved Sputnik V as the first vaccine for COVID-19. However, Phase 3 data on this vaccine have yet to be published. The approval has drawn criticism in the medical community due to lack of data on safety and efficacy. The institute has also made a preliminary presubmission of the vaccine in Brazil, which is required for its use in the country.

Gamaleya Sputnik V Official Report Data Internal & External Funding

This candidate is being supported by the Health Ministry of the Russian Federation

Notes & Status

Gamaleya’s candidate was the first registered vaccine released on the commercial market. Sudden release of trial data was seen as a pressured response to Pfizer’s results data announcement 2 days prior (Nov. 9)