Longitudinal study of SARS-CoV-2 antibodies following vaccination

Immunoglobulin G (IgG) antibody levels are correlated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with a greater immune response generating higher titers of neutralizing antibodies. Similarly, IgG levels could be utilized to indicate whether immunity has been achieved post-vaccination, though the relationship is still the subject of intense research.

A longitudinal study of IgG antibody levels in vaccinated healthcare workers was recently uploaded to the preprint server medRxiv*, suggesting that IgG levels could be a reliable indicator of successful vaccination.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

How was the study performed?

Historically, immunity by vaccination was confirmed in clinical trials over long periods of time and by long-term epidemiological studies. The current pandemic is urging the development of more rapid immunity testing technology, with potentially one of the most obvious indicators being the intensity of humoral response induced in an individual receiving a vaccine. The way in which the intensity of the humoral response is related to having acquired long-term protection, however, is not yet established. Additionally, preliminary studies have suggested that coronavirus disease 2019 (COVID-19) naïve individuals mount a significantly weaker immune response compared with those that have been previously infected with SARS-CoV-2, exhibiting lower antibody titers in the weeks following vaccination.

The group recruited 122 healthcare workers that had received the BioNTech-Pfizer vaccine in January, and blood samples were collected at this time and then regularly over a period of up to eight weeks, and the samples were applied to enzyme-linked immunosorbent assays (ELISA) against IgG. 36.1% of the participants had previously had and recovered from COVID-19, and this group was separated to observe any differences induced by past infection.

The influence of past SARS-CoV-2 infection

Following the first dose of the vaccine, the group that had previously recovered from COVID-19 showed a significantly more intense rise in IgG levels than the COVID-19 naïve group. However, the observation is reversed upon administration of the booster dose at day 21, with the COVID-19 naïve group seeing a much more significant increase. The group notes that the IgG levels across the COVID-19 naïve group are also far more homogenous compared with the much more varied response over time observed in those with pre-existing antibodies.

Overall, IgG antibody titers were higher amongst the COVID-19 experienced, particularly before receiving the booster dose. Within two days following the first dose, the COVID-19 experienced group exhibited a notable rise in IgG levels, with none detected amongst the naïve. On days 17-23, before receiving the second dose, the experienced group, on average, had around five times as much IgG in the blood. Upon receiving the second dose, the naïve group experienced a significant increase in IgG levels, though it still did not exceed the experienced group by day 70.

The researchers utilized two types of ELISA in the study, one of which detects IgG antibodies against the spike protein of SARS-CoV-2; the second detects the IgG antibodies against the nucleocapsid. The mRNA vaccine encodes for the spike protein of SARS-CoV-2, and thus anti-spike IgG production due to the vaccine was detected, while anti-nucleocapsid IgG was not. Interestingly, most of the pre-existing antibodies in the COVID-19 experienced group were against the nucleocapsid. These levels were approximately maintained throughout the rise of anti-spike IgG levels following vaccination. Eventually, these baseline anti-nucleocapsid IgG levels were seen to lower gradually by days 35-70 in the experienced group, though by this point it had been several months since infection.

The youngest participants experienced the quickest increase in IgG levels, though, among the COVID-19 experienced, those over 50 maintained the highest baseline IgG levels, meaning that they continuously bore IgG titers higher than other age groups.

The group determined that a past SARS-CoV-2 infection followed by one dose of vaccine produced larger quantities of strongly binding anti-spike IgG than two doses of vaccine in naïve individuals. This suggests that delaying the second dose might produce a more intense response in these individuals. A second longitudinal study composed of participants that have received only one dose of the vaccine could be beneficial for determining the optimal period. The group also plans to collect additional samples from the same participants involved in this study over a further period of six months, hoping to supplement these results with long-term IgG level data.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Apr 6 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Michael Greenwood

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Michael Greenwood

Michael graduated from the University of Salford with a Ph.D. in Biochemistry in 2023, and has keen research interests towards nanotechnology and its application to biological systems. Michael has written on a wide range of science communication and news topics within the life sciences and related fields since 2019, and engages extensively with current developments in journal publications.  

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