Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency

BackgroundThe antibody response after vaccination is impaired in common variable immunodeficiency (CVID).ObjectiveWe aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.MethodsIn an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD < 7.1) were compared by McNemar’s test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal–Wallis tests.ResultsAmong 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [−22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p < 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460).ConclusionMultiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination.Clinical ImplicationsBoosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.Capsule summaryThe third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders

HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (<350 cells/μl blood) and the ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART

Low morbidity in Danish patients with common variable immunodeficiency disorder infected with severe acute respiratory syndrome coronavirus 2

Manifestations and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well documented in patients with common variable immunodeficiency disorder (CVID). A Danish nationwide retrospective clinician-reported survey. Eleven patients with CVID and SARS-CoV-2 infection were identified. The median age was 50 years (range 22–72). All were on immunoglobulin replacement therapy. Eight patients had other pre-existing co-morbidities. Three patients were asymptomatic during the SARS-CoV-2 infection while seven developed mild coronavirus disease 2019 (COVID-19). One patient had more severe disease with hypoxia and required oxygen therapy. This patient had multiple co-morbidities including well known risk factors for severe COVID-19. All patients recovered. The results suggest that CVID may not be a risk factor for severe COVID-19. However, further monitoring of this immunodeficient population is needed to confirm our observation.</p

The frequency of CD16^pos NK cells increases with the duration of ART.

<p>A-B) The frequency of CD16^pos NK cells correlates with the duration of ART in years and with relative GzB activity. The total NK cell percentages and NK cell subsets are expressed as a percentage of the total lymphocytes. Linear regression curves with 95-confidence intervals are indicated. C) The individuals who had been treated for 5 years or more had significantly increased frequencies of CD16^pos NK cells compared to the individuals who had been treated for less than 5 years.</p

The frequency of CD16^pos NK cells expressing CCR7 correlates with the relative percentage of GzB activity.

<p>Correlation between the relative GzB activity mediated by PBM effector cells to the five phenotypic NK markers CCR7, NKp46, CD57, CD70 and CD27. A) The frequency of CD16^pos NK cells expressing CCR7 correlated inversely with relative GzB activity. B-E) No correlation was found between the frequency of CD16^pos NK cells expressing NKp46, CD57, CD70 and the relative GzB activity. The total NK cell percentages and NK cell subsets are expressed as a percentage of the total lymphocytes. Linear regression curves with 95-confidence intervals are indicated in each Figure.</p