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The Pfizer BioNTech vaccine for SARS-CoV-2

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 As the vaccine roll-out increases world-wide, one of the strongest candidates is the Pfizer BioNTech vaccine. A few facts assist with understanding the strength and value of this vaccine - 

• The Pfizer vaccine is designated as BNT162b2. 
• It is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein.
• Pfizer's method has been not to follow a traditional vaccine method that uses inactive, dead or portions of the actual virus to create an immune response but rather utilise mRNA to instruct human cells to develop their own spike protein similar to one found on the surface of coronavirus particles. The result is that a generation of antibodies are generated specifically targetted to the SAR-CoV-2 spike protein.
• The clinical trial had 43,548 participants in a multinational, placebo-controlled, observer-blinded, pivotal efficacy trial.
• The vaccine was trialed with each participant receiving two doses, 21 days apart.
• BNT162b2 was 95% effective in preventing COVID-19 and the efficacy was the same across all subgroups: age, sex, race, ethnicity, baseline body-mass index and co-existing conditions.
• Side effects were short-term including mild-to-moderate pain at the injection site, fatigue and headache.
• Of note, the Pfizer BioNTech vaccine can be stored up to 5 days at standard refrigerator temperatures when ready for use. It is essential however for very cold temperatures for initial shipping and longer storage.

The clinical trial results, peer reviewed are published in the New England Journal of Medicine (NEJM) which can be located at this link: Pfizer COVID vaccine results

Pfizer have a simple description of the vaccine on their website: Pfizer: the facts about Pfizer and BioNTechs COVID 19 vaccine

The terminology of viruses

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The coronavirus SARS-CoV-2 which causes COVID-19 will change over time and often terminology is inadvertantly misquoted in non-authoritative sources.  SARS-CoV-2 replicates itself by invading a new cell and fusing its genetic material termed RNA (or ribonucleic acid) into the new host. As the RNA is then duplicated, the new copy may not be an exact replica of the original virus.

In understanding the development of the virus changing into different forms, its worth distinguishing between the terms used to describe new versions of viruses generally -

• when an error occurs in duplicating viral RNA these changes are called mutations
• the viruses containing these mutations are termed variants (variants can have a single or many such mutations)
• when a variant virus shows distinct physical difference from the original parent virus, this is termed a strain. All strains are variants but not all variants are strains. 

COVID-19 and the challenges of mass population vaccination programs

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Pfizer-BioNTech, Oxford-AstraZeneca, Moderna, Johnson & Johnson - the vaccines that have been approved through 'Emergency Use Authorisation' in many jurisdictions across the world are rolling out. It's a mammoth effort involving a staggering number of individuals and inherent risks, some of which have already become apparent.

Global management consulting firm, McKinsey & Company, has assessed the process for vaccine roll-outs and identified six critical emerging risks, a number of which already exist in some form -

1. raw material constraints in production scaling: while there are early indications of sufficient global capacity for syringes and fill-finish materials, niche chemical and biological vaccine components are scattered. This creates the risk of competition between countries becoming reality and the challenges of supply which is created.
2. quality-assurance challenges in manufacturing: A new class of vaccines (such as those based on mRNA or viral vectors) at an unprecedented scale of 1.8 billion to 2.3 billion does by mid 2021 requires " massive volumes of inputs, a larger technical workforce, and much expanded ecosystem of production facilities".
3. cold-chain logistics and storage-management challenges: maintaining cold chain control for distribution and storage of mRNA-based vaccines will place strain on the production of dry-ice manufacturing. Fast distribution and usage of vaccines due to demand may alleviate some of this potential risk.
4. increased labour requirements: estimates show that the need for a trained workforce remains acute given the vaccination protocols which are complex in the handling and preparation of vaccines and the added care requirements for patients. Estimates suggest that COVID-19 vaccination is 3.5 times slower than the annual flu vaccination programs even with streamlined site management.
5. wastage at points of care: storing, preparing, scheduling administration of doses at points of care all have error risks. Perhaps the most significant is if there is product wastage when doses are not allocated sufficiently. Vaccine doses come in multidose vials and must be used in a short space of time.
6. IT challenges: Vaccine tracking system systems (VTrckS) or immunization information systems (IIS) designed to manage double doses in populations present software challenges. Given there has already been cyber attacks against COVID-19 vaccine developers and regulators, security has a whole new meaning.

The level of vaccination required is also vast with "..twice as many doses of COVID-19 vaccines being administered in one month than were administered for the whole of the 2009 H1N1 flu vaccine'' (McKinsey and Company 2021).  

McKinsey's propose a range of responses to the six critical emerging risks -

• scale manufacturing in new and existing facilities
• establishment of predictable supplier plans
• built-in redundancy into distribution
• leverage feedback loops
• use of several types of point-of-care facilities
• track and monitor spoilage at points of care
• pace first-dose allocation 
• balance IT upgrades and resilience 

A  link to the research article is below:

McKinsey & Company - the risks and challenges COVID 19 vaccine rollout 

SARS-CoV-2 - explaining the UK variant of the virus

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The emergence of three new variants of SARS-CoV-2 with what appears to be greater transmission amongst human populations again points to the manner in which viruses evolve and adapt in relatively short timespans. The new variants are from the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1).  

The engine of SARS-CoV-2 is its ribonucleic acid (or RNA) that is similar to human DNA but more primitive. SARS-CoV-2 spreads by binding to human cells through the spike proteins on its surface that allow it to penetrate cells and fuse its RNA into the target thus enabling it to replicate itself.

As the virus moves from population to population, this process of replication can and does lead to mutations occuring in the RNA which is then passed on to new hosts.

The UK strain of SARS-CoV-2 contains eight mutations to its spike protein of which three are of concern. These three mutations have been designated as -

• N501Y: which enables increased binding to human and murine ACE2 receptors (or the angiotensin-converting enzyme 2 which is found on the surface of human cells)
• 69-70del: which is traced to evolving from the outbreak in farmed minks
• P681H: which is associated with the furin cleavage site (FCS) in the spike protein and enhances what is known as "fusogenicity' or the ability to bind with other cells. The FCS in SARS-CoV-2 appears unique compared to other coronaviruses and more potent.

The efficacy of vaccines currently being deployed in respect of the new strains remains under investigation. The early data from vaccines produced by Johnson & Johnson, Oxford/AstraZeneca and Novavax is not as promising for the UK variant as the original virus although Pfizer appears to be effective. 

COVID-19 impact as at 31 January 2021

Johns Hopkins COVID-19 Dashboard

As COVID-19 continues its march across the globe with new strains emerging from the United Kingdom, South Africa and now Brazil, the continuing health burden remains critical. With 102.5 million confirmed cases worldwide, 2.2M deaths (of which the United States accounts for 439,000 followed by Brazil with 224,000) the vaccination program combined with public health measures (use of face masks, social distancing, use of hand sanitisers and on-site deep cleaning) remains the best course of action to bring the pandemic under control and ultimately end it.

SARS-CoV-2: effectiveness of the Oxford AstraZeneca vaccine

 

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Of the 58 vaccines under development to combat COVID-19, three vaccines so far have proceeded satisfactorily through the clinical trials process - one of these from the Oxford University - AstraZeneca partnership is scheduled for widespread inoculation of the Australian population during 2021 and onwards. This vaccine has been developed as a non-profit intervention aimed at "global supply, equity, and commitment to low-income and middle -income countries" (www.gavi.org/news) and has an agreement under the COVAX facility. Currently the vaccine is shown to have 70.4% efficacy.

Designated as ChAdOx1 nCoV-19, it utilises a chimpanzee adenovirus to enable a vectored vaccine. 

The four randomised controlled clinical trials of this vaccine took place in the UK, South Africa and Brazil with the UK and Brazil components being the first to report with interim efficacy results. Of note from these studies:

• 11, 636 participants were in the clinical trials
• 87.8% were aged 18-55 years
• 82.7% were white
• 60.5% were female

The phase 1 stage of the trial had supported a two dose regimen administered 28 days apart. There were no hospital admissions for those who received the vaccine whereas ten admissions occured in the control groups. An interesting development for the Oxford-AstraZeneca trial was the accidental provision of a low dose of the vaccine for some participants in the UK which was then boosted by a standard dose 28 days later that appears to have not reduced the level of effectiveness.

The clinical trials for this vaccine had substantial strengths including -

• a large sample size
• randomisation to vaccine groups
• inclusion of diverse sites with different races and ethnicities
• standardisation of key elements between trials
• balance of participant characteristics between the vaccine groups 
• similar results in Brazil and the UK for those receiving the standard dose regime providing credibility.

There have been limitations for the clinical trial studies as well such as -

• less than 4% of participants were older than 70 years of age
• no participants older than 55 years received the mixed dose regime
• unavailable results as yet on those participants with comorbidities and any impact.

The two dose regime poses its own challenges for health systems to coordinate and manage. A substantial practical advantage of the the Oxford AstraZeneca vaccine is that it can be transported and stored through the routine refrigerated cold chain whereas in contrast the Pfizer vaccine requires ultra-low temperature freezers.

[Information for this post has been drawn from The Lancet December 8, 2020]

A link is provided below.

Oxford- AstraZeneca vaccine - The Lancet