The UK’s successful vaccination strategy: why spacing out AstraZeneca doses between 8 and 12 weeks is key

On December 30, 2020, the MHRA (United Kingdom Healthcare and Medicine Products Regulation Agency) approved the Oxford-AstraZeneca vaccine with the modality that the second dose would be administered 3 months after the first. The same procedure was authorized for the Pfeizer BioNTech vaccine (which was approved on December 2). The reason given by the government was the need for the distribution of vaccines to be equitable: to vaccinate twice as many people with the (few) available vaccines..

This decision surprised many, so I decided to go back to basics and reread the study on the Oxford-AstraZeneca Phase III vaccine (published in Lancet on December 8). Pude allí confirmar that the decisión del MHRA había sido acertada: por razones de distribución de las dosis durante el ensayo llevado a cabo en UK, Brasil Y Sudáfrica, no todos los voluntarios del ensayo habían recibido la segunda dosis a las 4 semanas después de la first. Thus, in Table 3 of the works, it became evident that efficacy was 65.6% when the second dose was given 6 to 12 weeks after the first dose. In exchange was reduced to 53.4% ​​when the second dose was given before 6 weeks after the first dose.

The Kent variant, UK (B.117) is also more contagious and a little more deadly, more aggressive, but the vaccines work. The point is that with the Manaus variant, which has the E484K mutation, the vaccine does not work, it is very ineffective, and this is the important aspect. In this direction, Oxford is working on a new vaccine, to modify it to cover these new variants. But it wouldn’t be ready until October, because it is necessary to return to the laboratory phase.

It is important to note that this mutation appears simultaneously in several places of the globe, in South Africa, in the United Kingdom, in Brazil and in New York, in the United States, where some cases appeared a few weeks ago. As they arise in various places, it could be the natural evolution of the SARS-CoV-2 virus to acquire these mutations. In Argentina, if there are many infections, a local variant could hypothetically appear, with some of these mutations. What we do not know is if the ceiling of these mutations has been reached or if the virus can continue to evolve..

Given the current vaccine shortage, could a single dose be considered for the Oxford AstraZeneca vaccine? It is not approved. It would be irresponsible of me to lift it. What was done here in the UK was: there was X amount of millions of doses and it was said that not having two doses for all, twice the population received the first in January and the second dose was applied between 8 and 12 weeks later, i.e. the last injection was spaced three times months later. Immunity during this time is known to be even better if the second dose is applied a month after the first.

Space the second dose of Oxford AstraZeneca would be more effective. When the second dose is given after four weeks, the final immunity is approximately 53.4%, whereas if it is applied between 8 and 12 weeks, rises to more than 80%. This is the key piece of information. 22 days after the first dose is when you have maximum immunity, which lasts stable at 72% effectiveness for up to 3 months or 12 weeks. No one here in the UK is talking about applying a single dose.

Here, on December 30, this system was put in place: 8 to 12 weeks between doses. This gives 3 months of respite, the distribution of vaccines is maximized (here instead of vaccinating 13 million people, they vaccinated 26 million) since the vaccine is given to everyone during this time and also it was possible to drastically reduce the cases. According to this study, those immunized did not have serious complications, did not require hospitalization and did not die from COVID-19. There were some positives, among the medical staff for example, but they only had a headache.

And since there are fewer infections, there is also less possibility of mutation to the more aggressive strains.. And in addition, it is important since they took this modality of doses separated by 3 months with the strict schedule of the target population to whom it was a priority.

Simultaneously with the authorization of vaccines (Oxford AstraZeneca and Pfizer BioNTech with an interval of 3 months between doses) by the MHRA, the UK Joint Committee on Vaccination and Immunization (JCVI) created 4 priority orders of population at risk that should be vaccinated first:

-Adults over 80 in retirement homes and their assistants

-Adults over 80 in the community + frontline health and social services workers

-Adults over 75 (and other health personnel)

-Adults over 70, vulnerable people (including people with disabilities and their assistants).

On March 6, 2021, the prestigious Lancet magazine published a study and accompanying commentary which analyzed the results of the administration of the Oxford AstraZeneca vaccine with an interval of 12 weeks between the two doses in the United Kingdom. The study determined the effectiveness of this method: 22 days after the first dose, the vaccinated had obtained 76% immunity, which remained stable for 3 months. After the second dose, immunity increased to 81.3% (compared to 53.4% ​​when the second dose was before 6 weeks). One fact to highlight is that after 21 days of the first dose, there was no hospitalization for COVID-19. This shows the wisdom to vaccinate the community with 1 dose since the number of cases has decreased considerably: from 68,053 daily infections on January 8 to 5,758 new cases on March 17, from 1,890 deaths in January to 141 deaths on March 17 .

In 3 months, 27 million people were vaccinated, most with 1 dose (only 1.7 million with two doses), or 38% of the adult population. Cases, hospitalizations and deaths have been drastically reduced, by over 80%.

Recently I attended a seminar with the teacher Sharon peackock, Scientific advisor to the Prime Minister Boris Johnson, where he was presented: “COVID-19 mutations: past, present and future”. Two of the common concepts strongly impacted me:

1- The virus multiplies more easily in older people because their immune systems are weakened. The RNA (“the viral multiplication machinery”) of SARS-CoV-2 is defective, so that when the virus multiplies it exhibits many “replication errors” (mutations), with significantly greater chances than new variants appear (potentially the most contagious / fatal). The same would happen in other organisms with weakened immune systems, such as preexisting / disabled people. This happened in Kent, when on September 20 the British variant (B.117) appeared in an elderly person with a weak immune system. It follows that it is this population which must be privileged with the vaccine (in addition to the first line health personnel). People younger to be infected would be much less likely to create a new variant (strain), as the immune system in them is naturally strong (with this reasoning, the Priority Vaccination System has been implemented in the UK). United).

2- The variant that emerged in Manaus is characterized by the E484K mutation, which makes the virus more aggressive and more contagious.. An important fact is that the current vaccines are not very effective against E484K (they are being modified to cover variants with this mutation, and Oxford-AstraZeneca would be modified in October). This variant also appeared spontaneously in South Africa, New York and Bristol. This suggests that the acquisition of the E484K mutation could be the natural evolution of the virus. Therefore, it could occur spontaneously anywhere, in the event of infections in the population at risk. The strategic importance of vaccinating the largest number of the population is quickly being felt, to reduce infections and thus reduce the possibility of mutations and new variants.

The concepts mentioned above (1 and 2) support the need to adapt immunization practices: administration of two doses at an interval of 8 to 12 weeks and prefer vaccination to the elderly, pre-existing people, people with disabilities, their caregivers and frontline health workers.

The author, Marta Cohen, Argentinian pediatric pathologist -orunda de La Plata- currently works at Sheffield Children’s Hospital, UK. She was distinguished by the British Royalist Maximum with the Order of the Empire due to her work of more than a decade specializing in the investigation of the sudden death of breastfed children.