Durability of the neutralising effect of COVID-19 infection and/or vaccination

SARS-CoV-2 has pretty much affected all of us.

Some people have had mild COVID-19, but others have been very ill and required hospitalisation. Some people were vaccinated before they were infected, and others were vaccinated after being infected. Most people have been vaccinated two to three times with an mRNA vaccine.

Now a new study shows how different combinations of infection and vaccines subsequently affect the levels of the protective neutralising antibodies in the blood. The research shows that the individuals who required hospitalisation have since had a very high level of these neutralising antibodies and that booster vaccines send these levels back up again.

The research also shows that the antibody levels drop drastically following both infection and vaccination and that public health authorities offering booster vaccination starting in 2021 therefore probably made the right decision. They are associated with another large increase in the levels of these neutralising antibodies.

“Our results are important because they indicate the effect of booster vaccination versus not carrying this out. In that context, knowing how long the neutralising antibodies remain in your blood is important, because this indicates how well you are protected against COVID-19,” explains a researcher involved in the study, Jens Bukh, Director of the Copenhagen Hepatitis C Program (CO-HEP); Professor, Department of Immunology and Microbiology, University of Copenhagen; and Chief Research Physician, Department of Infectious Diseases, Amager and Hvidovre Hospital, Copenhagen.

The research has been published in the Lancet journal eBioMedicine.

Investigated the protective effect of infection and vaccines

The researchers examined the levels of neutralising antibodies in the blood at different times among individuals in various groups, including:

· non-hospitalised individuals who had COVID-19 and had later been vaccinated with an mRNA vaccine;

· hospitalised individuals who had COVID-19 and had later been vaccinated with an mRNA vaccine;

· individuals who had not had COVID-19 before being vaccinated with an mRNA vaccine; and

· individuals who were first vaccinated with a vector vaccine and then vaccinated with an mRNA vaccine.

The blood samples were taken about 1 month following infection or vaccination; after about 5–6 months; after 1 year; and, for some individuals, also after 2 years. All the vaccines were developed based on the original SARS-CoV-2 variant.

Severe illness provides better subsequent protection

The results show that regardless of whether the participants had been vaccinated against or had COVID-19, the levels of the neutralising antibodies in the blood increased and so did the protective effect. However, the various groups differed.

Non-hospitalised individuals who had COVID-19 had the least protection in the study. Conversely, individuals hospitalised with severe COVID-19 were better protected as were those who were vaccinated.

In all groups, the protective effect diminished over time, and after 6– 12 months whether any protection remained at all was questionable. However, individuals hospitalised with COVID-19 appeared to be slightly better protected over time as were individuals who had been vaccinated with two different vaccines.

Booster vaccination brought the levels of neutralising antibodies of all individuals up to a level offering good protection against COVID-19.

“Individuals hospitalised with COVID-19 had a higher level of protective antibodies in their blood, and these also remained higher over time compared with individuals with a relatively mild course of COVID-19 who had also been vaccinated,” says Jens Bukh.

Combination of infection and vaccination provides the best protection

Jens Bukh explains that it is interesting that the levels of the neutralising antibodies seem to follow the initial level of antibodies following the first exposure to the virus or the spike protein in vaccines.

Individuals with a high starting level resulting from severe infection experienced a reduction, but the level increased again for individuals then receiving booster vaccination. This did not diminish again to the same low level as seen for other combinations of infection and vaccination.

The researchers also found that the neutralising antibodies against the original variant of SARS-CoV-2 can also protect against other variants under the right circumstances.

Individuals only vaccinated against the original variant or only infected with the original variant are poorly protected against the Omicron variant, but individuals both previously infected and vaccinated have clear protection against not just the original variant but also against later variants.

“This is not surprising, because other studies have also shown that the combination of infection and vaccination gives the best protection, but this follow-up study of up to 2 years is the longest to date,” explains Jens Bukh.

Offering a fourth vaccination makes sense

Jens Bukh says that the results are relevant because they show that protection against COVID-19 is directly associated with the use of booster vaccines.

Public health authorities can use this knowledge when deciding whether to offer even more booster vaccinations to vulnerable individuals in the population or individuals older than 60 years who are at greater risk of developing severe COVID-19.

It is important to know how long a booster vaccine leaves sufficient neutralising antibodies in the blood. The study clearly indicates that the effect drops to potentially insufficient levels at about 6–12 months following vaccination.

“The study also suggests that deciding to offer a fourth vaccine injection in Denmark and elsewhere was a good decision. However, it is important to examine the effect of this fourth vaccination, which also includes Omicron, on the levels of the neutralising antibodies and its protective effect against several variants. We are investigating this,” concludes Jens Bukh.