by Ludwig Maximilian University of Munich

Study time chart, anti-spike IgG levels and IgG avidity in individuals with hematologic neoplasia and in healthy individuals at different time points after COVID-19 vaccination. a, Time chart of the study depicting time points of vaccination and blood sample collection in a cohort of individuals with hematologic cancers. Prevaccination samples were collected shortly before vaccination 1 (visit 1). Visit 2 occurred 2–8 weeks (median of 35 d) after vaccination 2. Visit 3 occurred 4–5 months (median of 149 d) after vaccination 2. Visit 4 occurred 2–8 weeks (median of 40 d) after vaccination 3. Vaccinations 1 and 2 were administered 6 weeks apart (median of 42 d); vaccinations 2 and 3 were 6 months apart (median of 189 d). b–d, Data are depicted as box plots with median, bounds between upper and lower quartiles and whiskers between the 10th and 90th percentiles. Differences between time points (visit 2, blue; visit 3, yellow; visit 4, red) were analyzed for statistical significance using the Kruskal–Wallis test with Dunn’s multiple-testing correction. Brackets show statistically significant differences, and precise numerical P values are indicated. Absence of brackets indicates absence of significance. b, Anti-spike S1 domain IgG titers in BAU per ml at different time points after vaccinations 2 and 3. The following samples were analyzed for groups of healthy individuals and individuals with hematologic neoplasia: 2–8 weeks after vaccination 2 (visit 2, blue; N = 21/N = 57), 4–5 months after vaccination 2 (visit 3, yellow; N = 20/N = 42) and 2–8 weeks after vaccination 3 (visit 4, red; N = 19/N = 42). c, Levels of antibody specific to the spike S1 domain after vaccinations 2 and 3 comparing subgroups of individuals with hematologic neoplasia; untreated LY (visit 2, N = 9; visit 3, N = 6; visit 4, N = 8)/LYs treated with Rx 12–60 months before receiving the first vaccination (Rx 12–60; visit 2, N = 9; visit 3, N = 7; visit 4, N = 6)/LYs treated with Rx in the last 12 months before the first vaccination (Rx < 12; visit 2, N = 14; visit 3, N = 10; visit 4, N = 9)/untreated MM (visit 2, N = 9; visit 3, N = 9; visit 4, N = 8)/treated MM (visit 2, N = 12; visit 3, N = 8; visit 4, N = 9). d, Avidity of anti-spike IgG at different time points after vaccinations 2 and 3; healthy individuals: visit 2 (N = 20)/visit 3 (N = 21)/visit 4 (N = 11); individuals with hematologic malignancies: visit 2 (N = 20)/visit 3 (N = 12)/visit 4 (N = 23). Credit: Nature Cancer (2022). DOI: 10.1038/s43018-022-00502-x

People suffering from blood cancer often have a weak immune system, putting them at higher risk of falling seriously ill with COVID-19. Some cancer therapies, moreover, result in these patients forming few or no antibodies against SARS-CoV-2 after COVID-19 vaccination. However, vaccination can also activate so-called T cells, which are responsible particularly for the long-term immune response.

A team led by physicians Dr. Andrea Keppler-Hafkemeyer and Dr. Christine Greil from the Medical Center-University of Freiburgand virologist Prof. Oliver T. Keppler from LMU Munich has now characterized in detail the course over several months of the immune response of patients with blood cancer who had received a total of three vaccinations against COVID-19. The results allow inferences to be made about the protection that vaccination gives these patients against serious illness from SARS-CoV2.

Strong T cell response to COVID-19 vaccination

The study focused on patients with two kinds of blood cancer: B-cell lymphoma and multiple myeloma. "Our results show that almost all study participants had a strong T cell response to COVID-19 vaccination," explains Dr. Andrea Keppler-Hafkemeyer.

"This could be one reason why breakthrough infections turned out to be mild to moderately severe even in study participants who had been unable to form any specific antibodies after vaccination because of their therapy," adds Dr. Christine Greil. The co-principal investigators and lead authors regularly look after blood cancer patients in the Department of Medicine I at the Medical Center—University of Freiburg.

The research group led by Prof. Oliver T. Keppler is specialized not only in analyzing the concentration of antibodies after vaccination, but also their quality. This depends particularly on the strength of the bonds between antibodies and the viral spike protein. In addition, the ability of antibodies to neutralize different SARS-CoV-2 variants in cell cultures plays a major role.

As the next step, therefore, the scientists compared the quantity and quality of antibodies and T cell responses to the spike protein among blood cancer patients and healthy study participants after two and three COVID-19 vaccinations.

High-quality antibodies against different SARS-CoV-2 variants

The study revealed that patients who can form antibodies tend to produce antibodies of particularly high quality. After their second vaccination, they are already able to neutralize and thus deactivate different SARS-CoV-2 variants. This ability is considerably more pronounced in this patient cohort than in vaccinated healthy people.

"COVID-19 vaccination can generate very broad antiviral immunity—including highly potent neutralizing antibodies—in patients with various types of blood cancer. Consequently, multiple vaccine doses can be recommended for patients with B-cell lymphoma or multiple myeloma without interrupting therapy," summarizes Prof. Oliver T. Keppler.

The paper is published in the journal Nature Cancer.

More information: Andrea Keppler-Hafkemeyer et al, Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma, Nature Cancer (2022). DOI: 10.1038/s43018-022-00502-x

Journal information: Nature Cancer 

Provided by Ludwig Maximilian University of Munich