Why a longer interval between COVID-19 vaccines may be more effective

With more than 97 million vaccines applied in Argentina and with a population that mostly already has two doses in its body and is in the process of applying the third and even fourth doses, a key question arises in the majority of the population. What is the ideal interval for getting a COVID-19 vaccine?

New research, which will be presented at this year's European Congress on Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon, has shown that a longer interval between primary doses of the COVID-19 vaccine can increase antibody production by up to 9-fold.

“Understanding the immune response to COVID-19 vaccination is essential to controlling the virus and reducing the number of deaths,” said the experts in charge of the work. To find out the factors affecting the antibody response following Pfizer/BioNTech COVID vaccination, Dr. Ashley Otter and his colleagues at the UK Health Security Agency (UKHSA) measured antibody levels in blood samples taken from nearly 6,000 healthcare workers across the UK enrolled in the SIREN study (SARS-CoV-2 Infection and Reinfection and Evaluation).

A total of 3,989 of the 5,871 participants received their first dose of the vaccine at least 21 days earlier. 1,882 had their second dose at least 14 days earlier. Participants were classified according to their history of infection as whether they had previously had COVID (confirmed by a PCR test or assumed due to their antibody profile) or naïve, i.e., no history of infection. Almost all (more than 99%) who had not had COVID seroconverted after vaccination, which means that they created antibodies to the virus.

After dose 1, those with a previous infection had antibody levels up to ten times higher than naïve individuals, while after dose 2, those with a previous infection had antibody levels more than twice as high as those who had not had a previous infection. When analyzing dosing intervals, it was found that a longer dosing interval was associated with up to nine-fold higher antibody levels in naïve participants over 10 weeks 11,479.73 with a more pronounced effect seen in younger participants. The dosing interval did not affect antibody levels in those with previous infection. However, a longer interval between infection and vaccination was associated with higher levels of antibodies.

Those who received the first dose of the vaccine eight months after infection had antibody levels seven times higher than those who were vaccinated three months after infection, with a plateau after eight months, suggesting that eight months after the primary infection may be an optimal time to receive first vaccine in those with previous infection. However, the analysis shows that, regardless of the time elapsed between infection and vaccination, all individuals have a very high antibody response after dose 2. In addition, women and persons belonging to an ethnic minority were associated with significantly higher antibody titers, while immunosuppression was associated with significantly lower post-vaccination antibody responses.

Dr. Otter points out that “this study shows that a longer time between dose 1 and dose 2 results in higher antibody responses in naive participants, which strongly supports the decision of the JCVI and the UK government to extend the interval between doses of the vaccine”. “We have also shown that in people with previous infection, the time between exposure and vaccination plays a key role in post-vaccination antibody responses,” he adds. However, further research is needed to determine whether these higher antibody levels provide greater protection against COVID-19 disease and how this longer dosing interval may affect booster responses.”

“Vaccines work by stimulating the immune system and inducing the production of specific antibodies against the disease in question,” explained Enrique Casanueva, head of Infectology Children at the Austral University Hospital. He added that there are different varieties of vaccines depending on how they are composed and that this also determines the patient's response. “People can react to vaccination, either because of the antigen they contain, because of the adjuvants or because of other substances present in them. The frequency of these reactions varies quite a bit between different vaccines, and that includes vaccines against COVID-19,” the expert said.

More research on intervals

A year ago, researchers from Australia provided a breakthrough to begin answering one of the most common questions around COVID-19 vaccines: how long protection lasts in the real world, and not in controlled trials. They conducted a study with predictive modeling techniques to estimate the robustness and duration of immune protection conferred by seven different vaccines for COVID. The results suggest that the longer it protects a vaccine immediately after it is administered, the longer its protection lasts. However, they warn that vaccination strategies would need to be adjusted to better address the problem of decreased immunity against coronavirus.

The scientists, led by Miles Davenport, from the Kirby Institute, which is based at the University of New South Wales in Sydney, Australia, based their model on the fundamental assumption that elevated levels of neutralizing antibodies - which are a subset of antibodies that can inactivate the virus - correlate with immune protection. This issue had arisen earlier in previous research on re-infection in patients recovered from Covid-19 and the safety and efficacy of the vaccine.

They used to carry out the study available data on vaccines produced by companies Pfizer-BioNTech, from the United States and Germany respectively; Moderna, from the USA; Sputnik-V, from Russia; Bharat Biotech, from India; Johnson & Johnson, from the United States; AstraZeneca; from England; and from Coronavac from Sinovac Biotech, from China. They were able to delineate the status of the levels of neutralizing antibodies generated by each of the vaccines over 250 days.

Another result of the work is that there would be differences in the levels of neutralizing antibodies depending on the vaccine applied. The Pfizer and Moderna vaccines were the most effective, with an initial efficacy of 95% that did not drop to 50% until about day 200. The Sputnik V vaccine maintained an efficacy of 70% at 150 days and 50% at 125 days. Meanwhile, the Johnson & Johnson and AstraZeneca vaccines had an initial efficacy of 67 and 62% respectively, but reached the 50% protection mark around day 50.

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