Study: Immune Response Varied Among COVID-19 Patients

Antibody and immune responses to SARS-CoV-2, the virus that causes COVID-19, varied substantially among convalescing patients, a small study found.

The plasma of 41 patients in Australia recovering from COVID-19 showed antibodies, memory B cells, and circulating follicular helper T cells against the SARS-CoV-2 spike glycoprotein, but there was a range of certain B and T cell responses and frequency among individuals, reported Stephen Kent, PhD, of the University of Melbourne in Australia, and colleagues, writing in Nature Medicine.

Why is this important for vaccine development? Because, Kent’s group said, “neutralization activity in the plasma ranges widely” despite the qualitative detection of major immune response markers.

“B and T cell responses targeting the [receptor-binding domain], and in particular the ACE2 interaction site, were markedly less frequent than total responses to [spike protein], to the point of being undetectable in some individuals,” they wrote.

And because the goal of a vaccine is to elicit neutralizing antibodies targeting the spike protein of the virus, which would prevent it from binding to ACE2 in human cells, this could have implications for “spike-based vaccine prototypes,” as it has been unclear how these models would work in humans, the authors added.

Patients in the study were adults with mild to moderate COVID-19 infection, with serological assays performed about a month after positive PCR tests for SARS-CoV-2. Median age of patients was 59, and 24 were men.

Spike-specific antibodies, memory B cells, and circulating follicular helper T cells were present in all participants. Neutralizing antibody titers were generally “modest,” which was “consistent with other reports in convalescent cohorts,” Kent and colleagues indicated.

But when analyzing how neutralizing activity correlated with specific cells, the authors found two inverse relationships. First, neutralization activity positively correlated with spike and receptor-binding domain antibody titers, spike- and receptor-binding domain-specific B cell frequencies, and spike-specific circulating follicular helper T cells, but was inversely correlated with a particular type of spike-specific follicular helper T cell expressing certain chemokine receptors.

A multiple regression analysis found high titers of spike-specific antibody and low proportions of spike-specific circulating follicular helper T cells with a certain phenotype as the most “significant predictive factors related to neutralization activity,” Kent and colleagues wrote.

Similar to recent reports, spike protein-specific antibody and spike protein-specific circulating follicular helper T cells were associated with participants’ reported severity of symptoms.

Limitations to the study include its small sample size and lack of epitope-level resolution. However, Kent’s group suggested their research could be a step towards developing biomarkers of immune function, specifically B cell and circulating follicular helper T cell frequencies and phenotypes, for clinical trials of new vaccines targeting the viral spike protein.