Credit ACIP/CDC
#15,616
Last July, in `Forward Looking' & `Aspirational' Vaccine Press Releases, we looked at many of the obstacles to the enormous task of producing and distributing a safe and effective COVID-19 vaccine in quantity, and on the timescales being touted by politicians and vaccine manufacturers.
For the HHS's `forward looking goals' of hundreds of millions of doses of vaccines to be made available before the end of 2020, absolutely everything would have to go perfectly. And it rarely does.
By November, those goals had been reduced to delivering roughly 40 million doses by the end of December (enough to immunize 20 million people). Whether that can still happen is unknown. But time is running short.
Yesterday, Australia's vaccine manufacturer CSL announced they were halting clinical trials of their COVID-19 vaccine - one which uses a non-infectious fragment of a glycoprotein (gp41) found in retroviruses - after several vaccine recipients developed false positive HIV tests.
No one actually developed HIV, or was injured by the vaccine, but the decision has been made to scuttle the project due to the confusion it would cause with future HIV testing.
Update on The University of Queensland COVID-19 vaccine
11 Dec 2020
Friday, 11th December, 2020: The University of Queensland (UQ) and CSL today announce that the Phase 1 trial of the UQ-CSL v451 COVID-19 vaccine has shown that it elicits a robust response towards the virus and has a strong safety profile. There were no serious adverse events or safety concerns reported in the 216 trial participants. However, following consultation with the Australian Government, CSL will not progress the vaccine candidate to Phase 2/3 clinical trials.
The University of Queensland commenced a Phase 1 trial of their COVID-19 vaccine candidate – v451 – in July 2020, to assess safety and immunogenicity in healthy volunteers. CSL was working towards taking responsibility for the Phase 2/3 clinical trial and large-scale manufacture of the vaccine, upon completion of successful trials.
The Phase 1 data also showed the generation of antibodies directed towards fragments of a protein (gp41), which is a component used to stabilise the vaccine. Trial participants were fully informed of the possibility of a partial immune response to this component, but it was unexpected that the levels induced would interfere with certain HIV tests.
On the heels of that report, overnight Sanofi and GSK announced a major delay - probably well into the second half of 2021 - in the delivery of their COVID-19 vaccine, after their formulation failed to produce an adequate immune response in older adults.
PRESS RELEASES
December 11 2020
- Phase 1/2 interim results showed an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years
- Insufficient response in older adults demonstrates the need to refine the concentration of antigen in order to provide high-level immune response across all age groups
- Companies plan a Phase 2b study with an improved antigen formulation
- With support from BARDA as part of Operation Warp Speed, study to start in February 2021, including a proposed comparison with an authorized COVID-19 vaccine
- Product availability now expected in Q4 2021 pending successful completion of the development plan
PARIS and LONDON – December 11, 2020 – Sanofi and GSK announce a delay in their adjuvanted recombinant protein-based COVID-19 vaccine program to improve immune response in older adults. Phase 1/2 study interim results showed an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years, but a low immune response in older adults likely due to an insufficient concentration of the antigen.
A recent challenge study in non-human primates performed with an improved antigen formulation demonstrated that the vaccine candidate could protect against lung pathology and lead to rapid viral clearance from the nasal passages and lungs, within 2 to 4 days. These results increase the Companies confidence in the capacity of the adjuvanted recombinant platform to deliver a highly efficient vaccine for all adults.
Sanofi’s recombinant technology and GSK’s pandemic adjuvant are established vaccine platforms that have proven successful against influenza. The recombinant technology offers the advantages of stability at temperatures used for routine vaccines, the ability to generate high and sustained immune responses, and the potential to prevent virus transmission.
“We care greatly about public health which is why we are disappointed by the delay announced today, but all our decisions are and will always be driven by science and data. We have identified the path forward and remain confident and committed to bringing a safe and efficacious COVID-19 vaccine. Following these results and the latest encouraging new preclinical data, we will now work to further optimize our candidate to achieve this goal,” said Thomas Triomphe, Executive Vice President and Head of Sanofi Pasteur. “No single pharma company can make it alone; the world needs more than one vaccine to fight the pandemic.”
Roger Connor, President of GSK Vaccines added: “The results of the study are not as we hoped. Based on previous experience and other collaborations, we are confident that GSK’s pandemic adjuvant system, when coupled with a COVID-19 antigen, can elicit a robust immune response with an acceptable reactogenicity profile. It is also clear that multiple vaccines will be needed to contain the pandemic. Our aim now is to work closely with our partner Sanofi to develop this vaccine, with an improved antigen formulation, for it to make a meaningful contribution to preventing COVID-19.”
The Companies plan a Phase 2b study expected to start in February 2021 with support from the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) under contract W15QKN-16-9-1002. The study will include a proposed comparison with an authorized COVID-19 vaccine. If data are positive, a global Phase 3 study could start in Q2 2021. Positive results from this study would lead to regulatory submissions in the second half of 2021, hence delaying the vaccine’s potential availability from mid-2021 to Q4 2021.
Sanofi and GSK adjuvanted recombinant protein-based vaccine candidate was selected in July 2020 by U.S. government’s Operation Warp Speed in order to accelerate its development and manufacturing.
The Companies have updated Governments and the European Commission where a contractual commitment to purchase the vaccine has been made.
Phase 1/2 study
The interim Phase 1/2 results showed a level of neutralizing antibody titers after two doses comparable to sera from patients who recovered from COVID-19, a balanced cellular response in adults aged 18 to 49 years, but insufficient neutralizing antibody titers in adults over the age of 50. The candidate showed transient but higher than expected levels of reactogenicity likely due to the suboptimal antigen formulation, with no serious adverse events related to the vaccine candidate. The most favorable results were observed in the group which tested the highest antigen concentration, combined with the GSK adjuvant, showing neutralization titers in 88% of participants. Seroconversion was observed in 89.6% of the 18 to 49 age group; 85% in the >50 age group; and 62.5% in the >60 age group.
The Phase 1/2 clinical study is a randomized, double blind and placebo-controlled study designed to evaluate the safety, reactogenicity and immunogenicity (immune response) of the COVID-19 vaccine candidate. A total of 441 healthy adults participated in the study, across 10 investigational sites in the United States. The participants received one or two doses of the vaccine candidate, or placebo at 21 days apart.
Full results of the Phase 1/2 study will be published as soon as all data are available, following peer-reviewed publication process.
Latest preclinical results
A recent preclinical study using a highly virulent challenge in non-human primates, showed high ability for the vaccine to protect against lung pathology and reduce virus in the nose and lungs within 2 to 4 days. Results from this pre-clinical study confirm strong ability of the vaccine candidate to stop the replication of the virus with an optimal antigen formulation.
These data are being prepared for submission to a peer-reviewed publication.
One of the reasons there are dozens of COVID vaccines under development around the world is the anticipation that not all of them will succeed. The fact that any vaccine has come off the assembly line, and is in the arms of HCWs before the end of 2020 is a remarkable achievement.
While I remain hopeful that hundreds of millions of people will be immunized against COVID-19 in the first half of 2021 - and that vaccines will eventually help blunt the impact of this pandemic - we are a long way from being out of the woods.
It would not be surprising to learn of additional setbacks in vaccine production, protection, or safety in the weeks and months ahead, and the logistics of getting a two-dose vaccine into the arms of literally billions of people are truly staggering.
I appreciate the `can do' attitude, and the willingness to swing for the fences when it comes to vaccine development and production, but there is something to be said for under-promising and over-delivering.
For now, the promise of a vaccine for the masses is still months away. Until that can become a reality, most of us will have to get through this winter relying on face covers, hand hygiene, social distancing, and a little luck.
