Vaccine doses: A changing medical approach

The Covid-19 pandemic triggered by the SARS-CoV-2 virus has substantially impacted humanity by causing about 200 million infections leading to more than 4 million deaths, not to mention an estimated $4 trillion in economic losses globally.

In addition to these direct and immediate impacts, there are also long-term repercussions: Covid-19 affects the health of infected and recovered individuals, especially those who have had severe symptoms, and may also cause mental health issues in some due to the social restrictions imposed to reduce the spread of infections.

This situation is made worse by the evolution of the parental SARS-CoV-2 into variants with increased infection potential and severe disease outcomes causing newer waves of infection, deaths and Covid-19-related restrictions. 

Overall, these have tremendously impacted the global healthcare system and, therefore, there have been extensive efforts by the scientific community around the world to come up with solutions to deal with the pandemic, the most anticipated of which is the development of vaccines, using both traditional methods and the novel method of using mRNA that expresses the viral protein.

Delaying doses 

These vaccines, available since late last year, showed very high levels of protection, albeit with some variations, in clinical trials. Subsequent studies have now revealed that these also protect against SARS-CoV-2 variants, including the Delta variant. 

However, an issue faced by a number of countries is the availability of a sufficient number of doses, that is the quantity of the vaccine to administer to the population.

This has been suggested as being largely due to the limited production capabilities as well as making them available at clinics. Therefore, some countries adopted a policy of delaying the second dose of the vaccine to vaccinate a greater portion of its population. This has raised some concerns about the effectiveness of the vaccines in protecting against the disease.

In order to address this issue, one needs to understand how vaccines work. Mimicking actual viruses, vaccines activate the immune system in our body that results in the production of the so-called ‘memory’ T and B lymphocytes/cells. The generation of the immune cells is what keeps an individual safe from the disease when the virus or any other pathogen infects him or her.

The development of the immune response towards a vaccine, including the mRNA-based ones, as shown in a recent publication from Qatar, typically takes about two weeks. Additionally, this time to achieve immunity may vary between vaccines given the differences in the way they activate the immune system i.e. the mechanism. 

Furthermore, following the initial immune response after the first dose (primary dose), many vaccines require a second exposure/shot (booster dose) for the development of a stable supply of memory immune cells for prolonged protection against the disease.

For instance, both mRNA-based Pfizer-BioNTech and Moderna vaccines and the Oxford-AstraZeneca’s vaccine require two shots while the Johnson & Johnson vaccine requires only one dose. 

As it turns out, a balance between the time required for the immune system to respond to the vaccine and the development of immunological memory is essential for the development of persistence of the memory cell for prolonged protection against the disease. If the immune system reacts too rapidly, then there will be little time for the development of the immunological memory.

Timing of doses 

Coming back to the question of the timing of the doses of vaccines that require two doses, it is necessary for us to realise that there is limited data available other than the currently available phase III trial data. For example, a single dose of the Pfizer-BioNTech vaccine provided 52 percent protection against Covid-19 while a second dose administered after three weeks increased the protection to 95 percent.

Another analysis performed as a part of the British Covid-19 infection survey indicated that both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines provided about 60 percent protection after the first dose and about 80 percent protection after the second dose. Yet another study has revealed that the Oxford-AstraZeneca vaccine provides around 76 percent protection after 22 days of the first dose while the number goes up to 81 percent after the second dose administered after 12 weeks of the first dose.

A recent study by a group of scientists from the University of Oxford including the Oxford COVID Vaccine Group indicates that a second dose of the Oxford-AstraZeneca vaccine after 10 months leads to the highest antibody presence, which is an indicator of protection provided by the vaccine with a caveat that the minimum amount or concentration of the antibodies required for developing protection against Covid-19 is not yet known.

However, such analysis and numbers regarding time periods or delays are not available for other vaccines, largely due to the limited amount of time that the vaccines have been around. These may become apparent with more studies undertaken in the future. 

It is also abundantly clear that even a single dose of these vaccines provides significant protection against Covid-19, although some experts in the area suggest that a second dose of the vaccines is required for the development of a robust immune response and memory.

Additionally, researchers have found significantly higher antibody levels and T-cell response after a third dose of the Oxford-AstraZeneca vaccine as compared to the second dose. This is important since a third dose of the vaccine resulted in higher antibody production after the third dose compared to the second against the Alpha, the Beta and the Delta variants.

To summarise, administration of both doses of the vaccines is advisable, for those that require it, at the tested intervals, if sufficient amounts/doses of the vaccines are available. 

If unavailable, a certain amount of delay in the second dose could be acceptable, and in the case of some vaccines, a delay could be even more beneficial against Covid-19.