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Review “on the field” about vaccines efficacy in England: are there hopes for a “single shot”?

The current outbreak of coronavirus disease 2019 (COVID-19) has caused a dramatic loss of human life and devastated the healthcare systems and socioeconomic structures of many countries globally. As an attempt to control the viral spread, several vaccines and therapeutics have been developed in record time. Some of these vaccines have also received emergency use approval from various national regulatory bodies authorities. In this context, the UK became the first country to roll out an mRNA-based COVID-19 vaccine developed by Pfizer and BioNTech (BNT162b2). Afterward, an adenovirus-based vaccine developed by the AstraZeneca (ChAdOx1) was also included in the UK’s COVID-19 vaccination program. The interim phase 3 clinical trial data indicate that both Pfizer and AstraZeneca vaccines are highly effective against SARS-CoV-2 when administered twice at intervals of 3 weeks and 4 weeks, respectively.  However, there is evidence suggesting that the level of protection can be improved by increasing the dosing interval.

Based on these findings, the UK Joint Committee on Vaccination and Immunization has recommended increasing the dosing interval up to 12 weeks for both vaccines. A team of scientists in the UK recently evaluated the effectiveness of the Pfizer and AstraZeneca vaccines against SARS-CoV-2 infection. The findings reveal that both vaccines are effective in significantly reducing SARS-CoV-2 infection in older adults and providing long-term protection. The current study was conducted to analyze the impacts of both Pfizer and AstraZeneca vaccines on confirmed COVID-19 patients aged 70 years and above. The efficacy of the vaccines in reducing emergency hospitalization and mortality has also been analyzed. Because the newly emerged B.1.1.7 variant has become the dominant strain in the UK, the vaccine effectiveness in managing this more infectious strain has been therefore analyzed.

The study findings revealed that a single dose of the Pfizer vaccine is 60-70% effective in reducing symptomatic SARS-CoV-2 infection among the older population in England; whereas, a two-dose vaccination regimen was found to be 85-90% efficacious. Regarding the AstraZeneca vaccine, a single vaccine dose is approximately 60-75% effective in reducing symptomatic infection. With the Pfizer vaccine, an effectiveness of 70% was observed after 28 days of first dose administration and an effectiveness of 90% was observed after 14 days of second dose administration. With the AstraZeneca vaccine, effectiveness of 60% was observed after 28 days of vaccination, which further increased to 75% after 35 days of vaccination.  Scientists estimated that compared to unvaccinated individuals, BNT162b2-vaccinated individuals who later on acquired SARS-CoV-2 infection had 44% and 51% lower risks of hospitalization and death, respectively. The AstraZeneca vaccine ChAdOx1 also showed some level of protection (37%) against hospitalization.     

During the initial phase of the roll-out, older people aged 80 years and above were the target population for vaccination. The scientists noticed that people vaccinated with the Pfizer vaccine during this phase had a higher rate of testing SARS-CoV-2 positive within a few days after vaccination. This indicates that the risk of COVID-19 is higher in the initially targeted population and that they may acquire infection before developing desired immune responses to the vaccine. The vaccine started providing protection after 10 – 13 days of immunization, which reached 70% after 28 – 34 days and remained constant. Scientists revealed that the B.1.1.7 variant of SARS-CoV-2 is currently predominating in England and that the variant has negligible influence on the vaccine effectiveness. The study findings collectively reveal that both Pfizer and AstraZeneca vaccines are effective in preventing SARS-CoV-2 infection and reducing COVID-19-related hospitalization.

A clear vaccine effect has been observed with a single dose, highlighting the option of maximizing the number of vaccinated people with a single dose to better manage the pandemic. Importantly, a significant proportion of vaccinated people have been found to develop SARS-CoV-2 infection, particularly during the first few weeks after vaccination. This highlights the importance of maintaining pandemic-related precautions even after vaccination. Based on available observations, many public health authorities have concluded that giving a single dose of the vaccine to the greatest possible number of people could spread the vaccine net wider, rather than ensuring that all those who receive the first dose also get the second within the stipulated interval. The assumption that a single vaccine dose can provide substantially effective protection is, however, highly controversial. Moreover, the fact that the clinical effect of two doses with the second dose being given after the stipulated interval was not studied in the clinical trials of these vaccines has raised considerable doubt as to whether they should be administered in this manner.

The vaccine’s ability to reduce asymptomatic transmission was also not a subject of investigation in these clinical trials. On the other hand, taking what is already known about vaccine immunology encourages the view that the single-dose assumption is valid, and clinical trial data on the Pfizer and Moderna vaccines has been re-analyzed to calculate the first-dose efficacy. The high figure of around 92% has led to the suggestion that a delayed second dose protocol be adapted to solve these issues and reduce the cumulative mortality. Further modeling is then necessary to understand how this change in strategy can impact mortality, the transmission network, and the case fatality rate, which can be at least two orders higher depending on the demographic group. time-bound simulation study shows that vaccination rates are key to determining the optimal vaccination strategy to reduce cumulative mortality as much as possible. At high vaccination rates of 1% a day, delayed doses are not associated with significant mortality benefits.

Similar is the case at low vaccination rates. However, with medium rates of vaccination, such as those seen in the USA at present, delaying the second doses except in those over 65 years is associated with a favorable result. Such information should help to promote delayed second dose strategies that could vastly extend vaccine coverage. A large number of subjects over a range of ages, and various interaction networks, in this simulation, helped to mirror human behavior in the real world. The period of 180 days chosen for most of the models was to facilitate its application to the current scenario. A delay in the second dose by up to six months is unlikely, based on current knowledge about vaccine-elicited immunity, to affect vaccine efficacy. This is supported by data from small studies on the delayed second dose administration of the Astra-Zeneca vaccine by 12 weeks or more, which has shown higher efficacy compared to the standard 21-day second dose schedule.

The next challenge is to boost population immunity without a dramatic rise in vaccine production rates in the near future.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it