COVID-19 vaccination in the UK: is it time to celebrate?

Over a year on from the first reported case of COVID-19, the UK has reported 3.32 million confirmed cases, and 88 590 people have died within 28 days of a positive COVID-19 test result (Public Health England (PHE), 2021).

The UK government has long claimed that vaccines are our best way out of this pandemic and towards a more normal way of life (Department of Health and Social Care (DHSC), 2021), and, although 2020 has been described as a difficult year, the UK has the accolade of being the first country in the world to commence a programme of vaccination against COVID-19.

This article reflects on the options for vaccination in the UK now, the features and benefits of each product and the rollout experience in the UK. The learning to date is reviewed to identify what more needs to be secured here and across the world before the ambition of a more normal way of life can be realised.

The race for a vaccine

COVID-19 is truly a global phenomenon: as of 16 January 2021, 92 262 621 confirmed cases of COVID-19 have been reported, and there is no continent, country or territory that remains unaffected (World Health Organization (WHO), 2021). The consequent socioeconomic devastation resulting from global infection is equally far-reaching and affects those already most vulnerable to inequitable standards of economic health (Buheji et al, 2020): estimates of the industrial consequences may appear beyond lay quantification. In May 2020, Lenzen et al (2020) valued the impact of COVID-19 counter-measures, such as travel restrictions and social lockdowns, the effect of worldwide reductions in production and consumption amplified by cascading impacts through international supply chains: the global consumption losses were estimated at $3.8 trillion, triggering significant job (147 million full-time equivalent) and income ($2.1 trillion) losses.

Non-technical solutions—restrictions on people movement, whole-community lockdowns, shutting of schools and universities, social distancing, requirements of face coverings in public places and hand hygiene—have not been enough to alter the unrelenting progression of this pandemic. The global health community has come to rely on technical responses to public health problems (Harrison and Wu, 2020), and the collaborative energy and resource of worldwide medical, research, commercial and political agencies has resulted in significant preventative therapeutic developments in an unprecedented timescale (Hanney et al, 2020). The UK has not hesitated to maximise the opportunity to change the future experience of coronavirus infection for its citizens, with vaccines having been approved for use in all four countries, and worldwide, a further 55 vaccines against SARS-CoV-2 are under development and in clinical trials (Knoll and Wonodi, 2021).

Vaccine options in the UK

There are three regulation 174-licensed options for vaccination against COVID-19 in the UK. First in gaining approval from the Medicines and Healthcare products Regulatory Agency (MHRA) was the Pfizer BioNTech mRNA Vaccine BNT162b2 (MHRA, 2020). Characterised as an mRNA vaccine, the genetic sequence for the spike protein found on the surface of the SARS-CoV-2 virus is encapsulated in lipid nanoparticles to support cell entry. Once injected into the recipient muscle, the mRNA is taken up by the host's cells, which translate the genetic information and reproduce the coding for the spike protein antigens on the surface of the cells. Nanoparticle function is more than just a carrier mechanism: these chemical envelopes are implicated in the potentiating of both adaptive (T and B cells) and innate (macrophages, monocytes and neutrophils) immune systems at the cellular level (Chauhan et al, 2020). Sustained immunity to SARS-CoV-2 occurs as a result of activation of the cell-mediated response, enabling T-cells to bind to and destroy any virus on future exposure, a critical element of any successful vaccination programme (Sauer and Harris, 2020).

Approved on 30 December 2020, COVID-19 Vaccine AstraZeneca uses a non-replicating viral vector as a carrier to deliver the RNA sequence for the SARS-CoV-2 virus spike protein into cells. The vector used is a weakened version of an adenovirus (responsible for causing common cold infection in chimpanzees), into which the genes that encode for the spike protein on the SARS-CoV-2 virus have been inserted (AstraZeneca, 2020). When this product ChAdOx1 nCoV-19 is injected, the host cells take up the vector, and the spike protein is then reproduced and expressed on the surface of the cells (Centres for Disease Control (CDC), 2021). This then stimulates the immune system to react by producing antibodies and memory T killer cells specific to the SARS-CoV-2 virus.

Most recently, a third option—COVID-19 Vaccine Moderna—has been granted licence under regulation 174 that gives authorisation for temporary supply by the UK DHSC and the MHRA (MHRA, 2021). Using similar mRNA technology as the Pfizer vaccine, the Moderna vaccine consists of a synthetically produced-and, therefore, cell-free-single-stranded copy of the RNA coding for the pre-fusion stabilised spike (S) glycoprotein of SARS-CoV-2. Prior research using nanoparticles for safe delivery of mRNA-coded information for the in vivo expression of a therapeutic protein in cancer treatments is an established technique that is considered natural, controllable and, as degradation of the mRNA follows uptake by the cells, transient (Probst et al, 2007).

Efficacy, safety and dosing

All three vaccination options exploit the natural process of a successful immune response were viral exposure to be uncontrolled in vivo. Priming the immune response by vaccination enables stimulation of innate activity of generic antiviral, anti-proliferative and immunomodulatory defences (Seth et al, 2006), supplemented by fast antigen-specific response from targeted memory cell-mediated production of antibody when future virus exposure occurs. Since disease cannot result from the newer mRNA and vector-borne vaccine methodologies, as they do not use live or attenuated virus, the vaccination process offers safety benefits over natural exposure to the coronavirus.

Detailed safety profiles of all vaccines are a primary concern during the earlier stages of vaccine trial phased development and, post rollout, PHE and the MHRA surveillance of the population experience remains an active process to ensure that the benefits of vaccination continues to outweigh risk (DHSC, 2021). In addition to this enhanced safety profile, a critical measure and primary objective of COVID-19 vaccine development is to demonstrate efficacy in preventing confirmed COVID-19 in those receiving the vaccine (Voysey et al, 2020; Clinical Trials Register, 2021).

Data from the clinical trials are used to inform dosing strategies to optimise maximum potency in population cohorts. Pooled analysis of data provides greater confidence for both efficacy and safety outcomes than can be achieved in individual studies and provides a broader understanding of the use of the vaccine in different populations (Voysey et al, 2021). For example, in the preliminary trials of the Oxford AstraZeneca COVID-19 vaccine, an unexpected increase in efficacy was observed in a subset of study participants who, owing to a measurement error, received less of the vaccine in the first of their two doses. The standard regimen-two doses of the same strength administered a month apart-had an efficacy of 62%, whereas the regimen with a lower initial dose yielded an efficacy of 90% (Ledford, 2020).

All available vaccines require a booster dose after 3 weeks to improve the efficacy and duration of the response (Folegatti et al, 2020; PHE, 2020; Polack et al, 2020). A two-dose regimen of the Pfizer BNT162b2 (30 μg per dose, given 21 days apart) was found to be safe and 95% (91% at least 7 days after the second dose) effective against COVID-19 (Polack et al, 2020).

In the interval between the first and second doses of the Pfizer vaccine, the observed vaccine efficacy against COVID-19 was almost half of that achieved by a second dose, at 52% (Polack et al, 2020). Nevertheless, the Joint Committee on Vaccination and Immunisation (JCVI) concluded that the first dose of either Pfizer BioNTech or the Oxford AstraZeneca vaccine provides substantial protection to an individual from severe COVID-19 disease within 2–3 weeks of vaccination (DHSC, 2021). A second dose is intrinsic to the approved schedule, although a minimum interval of 21 days between the doses of COVID-19 Pfizer mRNA Vaccine BNT162b2 and 28 days between the two doses of the AstraZeneca COVID-19 vaccine is required to achieve optimum immunogenicity and longer term protection.

In an effort to widen the coverage of a degree of protection achievable with one dose, UK vaccination schedules been amended in the short term to protect the greatest number of at-risk people in the shortest possible time (DHSC, 2021). To enable more people to receive a first dose of either vaccine, pending scaled-up manufacture feeding into the supply chain, the recommendation is that those receiving their first dose after 31 December 2020 should receive the second dose between 3 and 12 weeks later or in accordance with official guidance at the time (PHE, 2020). Public health economic modelling suggests that the incremental benefit of a second dose to those in receipt of the first dose is marginal versus the substantial initial protection to hitherto unvaccinated individuals, which is, in most cases, likely to raise them from 0% protected to 50%–70% protected, depending on the vaccine received and the subsequent immune response. The risk:benefit ratio is balanced, as these unvaccinated people are far more likely to end up severely ill, hospitalised or, in some cases, dying without a vaccine (DHSC, 2021).

MHRA approval recommends that COVID-19 Vaccine Moderna also be delivered as a two-dose regimen, with the doses administered 28 days apart. However, this schedule is yet to be reflected in the Green Book (PHE, 2020) or in the online E-Learning for Health portal training materials and assessments required of vaccinators in the UK.

UK vaccine rollout

Enormous effort has been put into underpinning the safety and accessibility of COVID vaccination, with whole-delivery system engagement, and this is entirely appropriate considering the nuanced differences in the available vaccines. In order to ensure the substantial access to vaccination, an NHS Bring Back Scheme has been initiated for recent retirees, and NHS leaders are working with partners, local authorities, health and social care partnerships and the voluntary sector to establish a prerequisite trained vaccination workforce of 80 000. In addition to mobilising the military and ancillary registered health professionals, such as opticians and dentists, with some relevant clinical skills, redundant cabin crew have been recruited for their non-clinical expertise in people and stock management in support of the mass vaccination agenda (DHSC, 2021).

The rollout of the vaccination is controlled by the Government, and access to vaccines is tightly restricted in line with the priority cohorts via pre-authorised NHS vaccination hubs. Prioritised populations have been established based on the primary intention of vaccination to reduce risk of developing COVID disease (Figure 1) and accessibility to vaccination. Advanced age and key pre-existing conditions are factors in risk stratification modelling that have informed the Government strategy of shielding the extremely clinically vulnerable (Clift et al, 2020). Data indicate that the absolute risk of mortality is higher in those aged older than 65 years than that seen in most younger adults with an underlying health condition (JCVI, 2020a).

Figure 1. Deaths within 28 days of positive COVID-19 test by date of death

The UK Government strategy for vaccine implementation is informed by the evidence to date that if all those in priority groups 1–9 were vaccinated, 99% of likely deaths from COVID disease could be prevented (Table 1). Evidence is clear that those living in residential and nursing care homes for older adults have been disproportionately affected by COVID-19, as they have a high risk of exposure to infection and are at higher clinical risk of severe disease and mortality (Clift et al, 2020). There is an increased risk of outbreaks, morbidity and mortality where older adults live in closed settings, exacerbated by environmental challenges, and there is an argument that prisons and places of detention should be included within the highest priority grouping in the UK and abroad (Siva, 2020).

The UK's COVID-19 vaccination is lauded as the biggest vaccination programme in NHS history (Table 2) (DHSC, 2021). Although variations exist in the four countries' approach to roll out, the principles are dominated by accessibility to and availability of the vaccines. The UK's vaccine portfolio was diversified across four different vaccine technologies to maximise the chances of finding a successful vaccine in advance of licensing approval. However, the lived experience to date suggests that the manufacture of the product and the glass vials as well as limited logistics including vaccinator availability are factors limiting optimal performance. Further, the characteristics of each of the vaccines mean that, although the JCVI does not advise a preference for either vaccine in any specific population, for operational and programmatic reasons to enable more extensive and timely vaccine coverage, one vaccine may be offered in certain settings in preference over another (JCVI, 2020b).

Necessarily, it has been large NHS trust sites and large-scale primary care network hubs that have been the initial recipients of the COVID-19 mRNA Vaccine BNT162b2 packs of 195 multi-dose clear-glass vials of vaccine due to the requirement to store undiluted vaccine in ultra-low temperature (ULT) freezers at –80°C to –60°C. Frozen packs containing 195 vials are removed to thaw at 2°C to 8°C, although undiluted vaccine has a maximum shelf-life of up to 5 days (120 hours) at 2 and 8°C. Once diluted, each reconstituted vaccine vial supplies 5 or 6 doses of 0.3 ml (30 μg product) and must be used within 6 hours (PHE, 2021). The pack size and the limited shelf-life warrant a pragmatic approach to ensure that the vaccine is not wasted. With this optimism, 138 000 people over the age of 80 years already in hospital or able to travel, as well as health and social care staff working on the frontline, had received a first dose of the Pfizer mRNA COVID-19 vaccine at GP-led or hospital vaccination sites by the end of 15 December 2020 (Haynes, 2020).

The AstraZeneca COVID vaccine is delivered in much smaller volumes: 80 dose packs (ten 4-ml vials with at least eight doses per vial) or 100 dose packs (ten 5-ml vials with at least 10 doses per vial) of a 0.5 ml dose (PHE, 2020). Maintenance of the cold chain between 2°C and 8°C prior to use remains as important with this vaccine as is usual practice with influenza vaccines. The shelf-life of an unopened multi-dose vial stored between 2°C and 8°C is 6 months. Once the vial bung is punctured, the COVID-19 Vaccine AstraZeneca must be used as soon as possible. It can, however, be stored between 2°C to 25°C for up to 6 hours, whereas the diluted Pfizer vaccine can only be stored at this temperature for up to 2 hours. The logistical challenges posed by the storage and distribution requirements for the Pfizer vaccine mean that, in some community-based populations, the AstraZeneca vaccine is the only one that will be deployed rapidly and without substantial vaccine wastage (JCVI, 2020b).

With access now to the AstraZeneca vaccine and the Moderna option, which requires frozen storage at normal freezer temperatures of –20°C, the UK Government's ambition to have completed vaccination of the top four priority groups identified by the JCVI by 15 February 2021 may yet be attainable.

Vaccine confidence and hesitancy

People in receipt of COVID-19 vaccination should be informed that it is critical to attend for their second dose in order to ensure lasting protection. However, the time delay between doses may amplify the phenomenon described by Harrison and Wu (2020) as ‘vaccine hesitancy’. Observed in 2019, for example, the CDC estimated that half of the US population did not get a seasonal influenza vaccine and, where vaccination has been the major influence in controlling outbreaks of infectious diseases, such as measles, failure of significant cohorts of the population to complete measles vaccination has resulted in escalating cases and mortality. The year before the pandemic, global coverage with the first dose of measles vaccine stalled at 85%. Although not close to the required 95% coverage required to prevent outbreaks, the failure to achieve second dose coverage at 67% provides opportunity for new host exposure for the virus to impact vaccinated communities (WHO, 2020a).

In phase III trial data, the Pfizer BNT162b2 vaccine was found to be 95% effective in preventing COVID-19 (95% credible interval, 90.3–97.6), and similar vaccine efficacy (generally, 90–100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index and the presence of coexisting conditions (Polack et al, 2020). This is great news for those concerned about the most vulnerable to COVID-19 in society (PHE, 2020b). However, the >90% efficacy of the vaccines in clinical trials in vivo is entirely dependent on completion of the advisory vaccination two-dose schedule by those invited to receive vaccination. To reduce this risk, clear instructions and the rationale behind the COVID-19 vaccination scheduling policy is included in free, standard patient information and vaccination record cards, and it should be used to support uptake of the second dose of, preferably, the same vaccine. The Government has launched a public health campaign targeted to engage the social contract, a sense of public responsibility to offer practical support to ensure the success of the vaccination programme in order to achieve the required herd or community immunity (PHE, 2021b).

Mass COVID-19 vaccination would mean fewer people with the disease and, hence, less virus replication and spread. It is scientifically plausible to anticipate a subsequent reduction in transmission. An earlier indicator than the measures of people admitted to hospital with symptoms or dying within 28 days of a positive test result (PHE, 2021) would be decreasing the number of people testing positive for the virus; yet, the evidence for this impact on transmission of the virus is pending.

The future

Vaccines work (Folegatti et al, 2020; Polack et al, 2020), yet for COVID vaccination to truly herald a turning point in the pandemic experience and allow economies, education and health provision to begin recovery, a significant proportion of the global population must have effective immunity so that reservoirs of new vulnerable hosts are not available to facilitate transmission of dominant or virulent new variants. Viral vector vaccines illicit a strong immune response, have superior protein expression and prolonged stability (Chauhan et al, 2020), but the success of any rollout programme where infrastructure is compromised is probably entirely dependent on securing adequate storage, logistics, manufacture and refrigerated transport delivery systems.

It is not yet known how long protection from vaccination will last: antibody and memory T cell seroprevalence studies over time may inform of the level of chemical and cell immune response that prevents COVID-19 (Moore, 2020) or whether regular booster doses will be needed to maintain effective immunity, as is the case annually for the flu virus (PHE, 2020).

Naturally, recipients will be diverse in their ability to develop an effective and lasting immune response. Compromised immune systems and high risk of disease in the older population may warrant adjuvant strategies to manipulate the magnitude and longevity of the immune response to ensure lasting protection. Adjuvanted flu vaccination for the over 65s is described in the Green Book; it affects higher immunogenicity by optimising the activation of CD4+ and CD8+T cell response to improve the long-term efficacy of vaccines (Chauhan et al, 2020; Liang et al 2020; PHE, 2020). The immune-stimulatory properties of mRNA may need to be enhanced by the inclusion of an adjuvant to increase the potency of some mRNA COVID-19 vaccines (Pardi et al, 2020).

It is not yet known how and when vaccination of a cohort will shape transmission rates or whether it will merely prevent individual progression to COVID-19.

Andrew Pollard, chair of the UK's JCVI and the European Medicines Agency's scientific advisory group on vaccines, recognises the vaccines may need to be altered in the event that the virus drifts into a new variant against which the vaccines are not effective and describes the capacity for tweaking the RNA/DNA components of the mRNA and vector vaccines to meet the threat of an emerging variant SARS-CoV-2 (Mahase, 2021).

On 14 December 2020, the UK reported a variant referred to as SARS-CoV-2 VOC 202012/01. As of 30 December 2020, this variant had been reported in 31 other countries or territories in five of the six WHO regions, and a further variant with a similar N501Y mutation was identified on 18 December 2020 in South Africa. With the nomenclature of 501Y.V2, this phylogenetically unrelated strain has been reported in four other countries to date (WHO, 2020b). Although suggestive of increased transmissibility, there is no indication that these variants cause more severe disease or worse outcomes. Epidemiological and virological studies are ongoing to explore whether the relevance of one of the mutations (N501Y) in the receptor-binding domain, found in both the SARS-CoV-2 VOC 202012/01 and 501Y. V2 variants will influence the efficacy of the vaccines in an exposed cohort (Volz et al, 2020). The development of effective vaccines will be a continuing feature of planned pandemic prevention (DHSC, 2021).

Vaccine administration data will continue to yield information and detail, which will inform future planning and fine-tuning of the vaccines in production, including efficacy against the evolving variant strains of SARS-CoV-2. The opportunity for variant virulent species to evolve and repeatedly threaten world stability persists.

Knoll and Wonodi (2021) make the point that, despite the good news in the UK, COVID-19 cases are at their highest daily levels globally. The greatest challenge now may be to commit to social contract and discharge international responsibility to heal the rest of the world. Without global access to vaccination, borders remain shut, trade is constrained and millions more will be consumed by poverty.

Conclusion

The COVID-19 pandemic is out of Pandora's box: the real test of global security now requires a focus on communicable disease prevention. As the earliest beneficiary of the global vaccine development, the UK has a social obligation to mobilise its recovery into understanding the wider environmental and human factors that may have influenced the conditions that contributed to the zoonotic evolution of the novel pathogen. In the interest of humankind, the principles of intelligent infection prevention must be applied to scrutinise the behaviours that upset the natural world order and to nurture the ecological microbiome that there is a universal responsibility to respectfully maintain for future generations.