South African Gov. Halts Temporarily Oxford Vaccine Trial In South Africa Due to Low Efficacy Against the South African Variant

South African Gov. Halts Temporarily Oxford Vaccine Trial In South Africa Due to Low Efficacy Against the South African Variant TrialsiteN

The South African government, via South Africa Health Minister Dr. Zweli Mkhize, declared a temporary hold on the AstraZeneca (Oxford) vaccine studies in that nation apparently because of the candidate’s low efficacy against the South African variant strain of SARS-CoV-2. While one of the original developers of the vaccine from Oxford, Prof. Sarah Gilbert suggests the vaccine should still protect against severe disease, it’s clear that vaccine developers may need to develop a modified version of the injection targeting this mutant named 501.V2 or B.1.351. In concerning events, the E484K mutant, which includes the South African variant, has been reported as of late as an “escape mutation” not effective in one form of monoclonal antibody against the coronavirus, suggesting a “Possible change in antigenicity.”  Does this mean that in all reality the AstraZeneca vaccine should be reformulated for this E484K mutation immediately? This mutation also exists in the P.1. and the latest UK variant. Since there are multiple variants of SARS-CoV-circulating now, AstraZeneca may consider a multivalent vaccine. In the short run, the health authorities confirm diversification of access to vaccine products, including confirmation of orders for Johnson and Johnson as well as Pfizer (BioNTech). On the other hand, prominent figures involved suggest a “recalibration of thinking” in regards to the vaccine paradigm—perhaps transitioning from an ideal target of herd immunity against transmission to a far more targeted risk-based approach to national vaccination.

The Situation

The overseer of the South African Oxford COVID-19 clinical trial in South Africa, the Wits Vaccines and Infectious Diseases Analytics (VIDA) Research Unit, recently reported that in an analysis submitted to preprint server and thus pre-review finds that a two-dose regimen of the ChAdOx1 nCoV-19 (AZD1222) vaccine only provides minimal protection against mild-moderate COVID-19 infection from the B.1.351 South African variant first identified just in mid-November 2020.

The team at Wit didn’t assess the efficacy against severe SARS-CoV-2. While the vaccine did demonstrate a high efficacy against the original non variant COVID-19 in South Africa, unfortunately the concern here is that if the vaccine cannot effectively prevent mild and moderate versions (the great majority of cases—there is a problem). 

The researchers, both from South Africa and the UK, discovered that actual vial neutralization by the Oxford vaccine targeting B.1.351 were “substantially reduced when compared with the ‘original’ strain of the coronavirus.”

A temporary halt, as reported in STAT by Matthew Herper, Salim Abdool Karin, an epidemiologist from Columbia University and advisor to the South African government, was quoted, “The AstraZeneca vaccine rollout needs to be put on temporary halt while we get the clinical efficacy information in.”  He continued, “And the way that we do that is with the new approach to rollout.”

What’s the Problem?

Based on this data set now on its way for scientific review, scientists now can make at least the theoretical argument that mutations such as the one seen in South Africa actually facilitate the ongoing transmission of COVID-19 in vaccinated populations. This is actually the case with reports of those with prior infection re-infected.

The British press sought to reduce the impact of this news—for example, Edward Argar, UK Minister of State for Health informed the news outlet Sky that, “There is no evidence that this vaccine is not effective in preventing hospitalization and severe illness and death, which ultimately is what we’re seeking with these vaccines today.”  He went on that at least in the UK the South African strain is by any means dominant among SARS-CoV-2 strains, noting there is the “historic one we’ve had, and then the Kent variant, against which this vaccine is highly effective.”

But in South Africa, the halt, at least temporarily, is in place. 

The Study

The study involved approximately 2,000 volunteers with a median age of 31. The study team defined mild disease as one with at least one COVID-19 based symptom. As the target population were at low risk, the study team couldn’t assess rates of protection against moderate-severe disease, hospitalization or death.

Principal Investigator Point of View

Shabir Madhi, Professor of Vaccinology and Director of the Vaccines & Infectious Diseases Analytics (VIDA) Research Unit at University of the Witwatersrand and Chief Investigator on the trial in South Africa, reported, “Recent data from a study in South Africa sponsored by Janssen which assessed moderate to severe disease, rather than mild disease, using a similar viral vector, indicated that protection against these important disease endpoints was preserved. This could be relevant to the ChAdOx1 nCoV-19 vaccine, which has been developed using similar technology as the Janssen vaccine, and for which the vaccine induced immune responses are also similar. “

‘”These findings also force us to recalibrate thinking about how to approach the pandemic virus and shift the focus from the aspirational goal of herd immunity against transmission to the protection of all at risk individuals in the population against severe disease.”

The Chief Investigator of the Oxford vaccine trial, Andrew Pollard, Professor of Pediatric Infection and Immunity, shared, “This study confirms that the pandemic coronavirus will find ways to continue to spread in vaccinated populations, as expected, but taken with the promising results from other studies in South Africa, such as those using a similar viral vector, vaccines may continue to ease the toll on health care systems by preventing severe disease.”

Oxford at Work

As a result of these growing problems, University of Oxford in association with partners such as AstraZeneca and Serum Institute of India seek to potentially develop a second generation of the ChAdOx1 nCoV-19 vaccine, adapted to target variants such as B.1.351.

Work is already underway at the University of Oxford and in conjunction with partners to produce a 2nd generation of the vaccine, which has been adapted to target variants of the coronavirus with mutations similar to B.1.351, if it should prove necessary to do so.

South Africa Moving to Secure Johnson & Johnson Vaccine Product

South Africa Health Minister Dr. Zweli Mkhize reports in the local news that a planned batch of Johnson & Johnson’s vaccine would be available for vaccinations next week. Apparently. this country is hedging its plans against the Oxford/AstraZeneca vaccine as Dr. Mkhize declared, “The most important thing was to find an alternative to ensure our plan doesn’t derail. We have been able to achieve that partly, we have reached out to other companies, so that we can bring forward the Johnson and Johnson vaccine which we have ordered from them and we are also going to bring forward the Pfizer vaccine. The issue for us is that the vaccination program continues.”

About the Wits Vaccines & Infectious Disease Analytics (VIDA) Research Unit

Formerly known as the Respiratory and Meningeal Pathogens Research Unit (RMPRU) and founded in 1995, the Vaccines and Infectious Diseases Analytics (VIDA) Research Unit of the University of the Witwatersrand (Wits) is an internationally recognized, African-led research unit in the field of epidemiology of vaccine preventable diseases, and clinical development of life-saving vaccines.

Under the guidance of Professor Shabir Madhi, a global leader in the field of pediatric infectious diseases and the Dean of the Faculty of Health Sciences at Wits University, Wits VIDA is conducting translational research on vaccine preventable diseases and training the next generation of clinician scientists. Combining clinical, microbiological, and epidemiological expertise in an African setting, Wits VIDA’s cutting-edge scientific research informs local and global policy recommendations on the use of next-generation and novel vaccines today. In addition to various other studies on COVID-19, Wits VIDA championed and led the first two COVID-19 vaccine trials in Africa in 2020, for the Oxford and Novavax vaccine candidates.

Unchecked UK Strain Exponential Growth Could Lead to Next Deadly Wave

In the meantime, reports are in that the UK strain is doubling in America every ten days. The recent study, utilizing a Centers for Disease Control and Prevention (CDC) model, reveals that this mutant strain while still the small minority, won’t be if this doubling every ten days continues. Although the study authors believe the U.S. still has time to act and slow down this rapidly growing strain, they warned without “decisive and immediate public health action,” this variant “will likely have devastating consequences to COVID-19 mortality and morbidity in the U.S. in a few months,” reports CNBC.

Lead Research/Investigator

Andrew Pollard, BSc MBBS PhD (Lond), DIC, MRCP (UK), FHEA, FIDSA, FRCPCH, MA, FMedSci, Professor of Pediatric Infection and Immunity

Shabir Madhi, M.B.B.C.H., FCPaeds(SA), Ph.D., Professor of Vaccinology and Director of the Vaccines & Infectious Diseases Analytics (VIDA) Research Unit at University of the Witwatersrand and Chief Investigator

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