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. 2023 Feb 18;11(2):480.
doi: 10.3390/vaccines11020480.

Assessment of the Interferon-Lambda-3 Polymorphism in the Antibody Response to COVID-19 in Older Adults Seropositive for CMV

Ariane Nardy  1 , Camila Tussato Soares Camargo  1 , Yasmim Faustina Castro de Oliveira  1 , Fernanda Cristina da Silva  1 , Millena Soares de Almeida  1 , Fernanda Rodrigues Monteiro  2 , Brenda Rodrigues Silva  2 , Jônatas Bussador do Amaral  3 , Danielle Bruna Leal Oliveira  4   5 , Edison Luiz Durigon  5   6 , Guilherme Pereira Scagion  5 , Vanessa Nascimento Chalup  5 , Érika Donizetti Candido  5 , Andressa Simões Aguiar  5   7 , Neil Ferreira Novo  2 , Marina Tiemi Shio  2 , Carolina Nunes França  2 , Luiz Henrique da Silva Nali  2 , André Luis Lacerda Bachi  2
Affiliations

Assessment of the Interferon-Lambda-3 Polymorphism in the Antibody Response to COVID-19 in Older Adults Seropositive for CMV

Ariane Nardy et al. Vaccines (Basel). .

Abstract

Background: Here, we investigated the impact of IFN-lambda-3 polymorphism on specific IgG responses for COVID-19 in older adults seropositive for CMV.

Methods: Blood samples of 25 older adults of both sexes were obtained at three different times: during a micro-outbreak (MO) of SARS-CoV-2 in 2020; eight months after (CURE); and 30 days after the administration of the second dose of ChadOx-1 vaccine (VAC). The specific IgG for both SARS-CoV-2 and CMV antigens, neutralizing antibodies against SARS-CoV-2, and also the polymorphism profile for IFN-lambda-3 (rs12979860 C > T) were assessed.

Results: Higher levels of specific IgG for SARS-CoV-2 antigens were found in the MO and VAC than in the CURE time-point. Volunteers with specific neutralizing antibodies against SARS-CoV-2 showed better specific IgG responses for SARS-CoV-2 and lower specific IgG levels for CMV than volunteers without specific neutralizing antibodies. Significant negative correlations between the specific IgG levels for SARS-CoV-2 and CMV were found at the MO time-point, as well as in the group of individuals homozygous for allele 1 (C/C) in the MO time-point and heterozygotes (C/T) in the CURE time-point.

Conclusion: Our results suggested that both CMV seropositivity and the homozygosis for allele 1 (C/C) in IFN-lambda-3 gene can negatively impact the antibody response to COVID-19 infection and vaccination in older adults.

Keywords: SARS-CoV-2; allele; cytomegalovirus; immunoglobulins; neutralizing antibody; outbreak.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total serum levels of IgG specific for SARS-CoV-2 (O.D. 450 nm—(A)) and CMV (UI/mL—(C)) antigens, and the dynamics of serum IgG levels for SARS-CoV-2 (B), in a group of older adults who participated in the study on three different occasions: during the micro-outbreak of SARS-CoV-2 infection (MO), 6–8 months after this infection (CURE), and 30 days after administration of the second dose of ChadOx-1 vaccine (VAC). Also presented here are the total serum levels of IgG specific for SARS-CoV-2 (O.D. 450 nm—(D)) and CMV (O.D. 450 nm—(E)) antigens when the volunteers were separated in accordance with the presence (R—responders) and not (NR—non-responders) of neutralizing antibodies for SARS-CoV-2. * denotes values of p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 2
Figure 2
Total serum levels of IgG specific for SARS-CoV-2 (O.D. 450 nm—(A)) and CMV (UI/mL—(B)) antigens in the group of older adults who participated in the study separated in the subgroups of “men” and “women” on three different occasions: during the micro-outbreak of SARS-CoV-2 infection (MO), 6–8 months after this infection (CURE), and 30 days after administration of the second dose of ChadOx-1 vaccine (VAC). * denotes values of p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 3
Figure 3
Spearman coefficient correlation analysis between total serum levels of CMV-specific IgG (IU/mL) and COVID-19-specific IgG (O.D. 450 nm) in the older adults who participated in the study on three different occasions: during the micro-outbreak of SARS-CoV-2 infection (MO, (A)), 6–8 months after this infection (CURE, (B)), and 30 days after administration of the second dose of ChadOx-1 vaccine (VAC, (C)).
Figure 4
Figure 4
Representative graphic of allelic discrimination obtained after the genotyping assay for polymorphism in the il28b gene (rs12979860) in the older adults who participated in the study. In red color are presented the volunteers homozygous for allele 1, which corresponds to the nitrogenous base cytosine. In blue are presented the volunteers homozygous for allele 2, corresponding to the nitrogenous base thymine. In green are presented the heterozygous volunteers.
Figure 5
Figure 5
Total serum levels of IgG specific for SARS-CoV-2 (O.D. 450 nm, (A)) and CMV (UI/mL, (C)) antigens in the subgroups of volunteers grouped in accordance with the polymorphism in the IFN-lambda gene [allele 1 (C/C), allele 2 (T/T), and alleles 1 and 2 (heterozygous, C/T)], as well as these levels in the same subgroups of volunteers separated in accordance with the presence (R—responders) or not (NR—non-responders) of neutralizing antibodies for SARS-CoV-2, respectively (SARS-CoV-2—(B) and CMV—(D)). * denotes values of p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 6
Figure 6
Spearman coefficient correlation analysis between total serum levels of CMV-specific IgG (IU/mL) and COVID-19 IgG (O.D. 450 nm) in the volunteers grouped in accordance with the polymorphism in the IFN-lambda gene [allele 1 (C/C), allele 2 (T/T), and alleles 1 and 2 (heterozygous, C/T)], on three different occasions: during the micro-outbreak of SARS-CoV-2 infection (MO—(A–C), respectively), 6–8 months after this infection (CURE—(D–F), respectively), and 30 days after administration of the second dose of ChadOx-1 vaccine (VAC—(G–I), respectively).
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