The ongoing Covid-19 pandemic underscores the importance of finding effective and safe ways to combat the virus, and to optimally understand the immune response elicited upon natural infection. This likely involves all components of the immune system, both innate and adaptive. The impetus for the rapid development of prophylactic treatment options has led to an intense focus on neutralizing antibodies (Abs), and many novel and specialized platforms have been designed to achieve that goal. B-cell immunity relies on the generation of a diverse repertoire of Abs. Their structural variation is defined in terms of amino acid composition that is encoded in the genome or acquired through somatic mutations. Yet, key examples of frequently neglected antibody diversification mechanisms involving post-translational modifications such as N- or O-linked glycosylation are present in significant portions of the population. During the last few years, these and other beyond gene sequence determined humoral immune response mechanisms have in some specific cases revealed their potent immunomodulatory effects. Nonetheless, such more unusual mechanisms have not received much attention in the context of SARS-CoV-2. Thus, with specific focus on the latter, this paper presents, (1) the rationale for considering beyond sequence determined strategies, (2) evidence for their possible involvement in Covid-19 disease evolution, (3) consequences for vaccine design exemplified by one of the vaccine candidates that is currently undergoing trial, and (4) more general implications. Based on a critical interpretation of published literature, the hypotheses developed in this study point to a crucial role of non-genetic antibody diversification mechanisms in disease evolution to counteract unique immunogenicity determinants of SARS-CoV-2 infection. The involvement of post translational mechanisms may also help explain the widely varied immune response observed, not only among different patient groups, but also in terms of their observed incompatibility with SARS-CoV-2 infection in several human cell types. The article highlights potentials and challenges of these refined humoral immune response mechanisms to most optimally target non-genetic viral evasion strategies.
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http://dx.doi.org/10.3389/fphys.2021.624675 | DOI Listing |
J Infect Dev Ctries
December 2024
Students' Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
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View Article and Find Full Text PDFExpert Rev Mol Diagn
January 2025
Department of Pediatrics, Polytechnic University of Marche, Ancona, Italy.
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View Article and Find Full Text PDFMol Plant
January 2025
College of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing, China. Electronic address:
Plants possess remarkably durable resistance against non-adapted pathogens in nature. However, the molecular mechanisms underlying this resistance remain poorly understood, and it is unclear how the resistance is maintained without coevolution between hosts and the non-adapted pathogens. In this study, we used Phytophthora sojae (Ps), a non-adapted pathogen of N.
View Article and Find Full Text PDFVirol J
January 2025
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China.
Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5).
View Article and Find Full Text PDFBiol Sex Differ
January 2025
Department of Psychology, Memorial University of Newfoundland and Labrador, St. John's NL, Canada.
As the earliest measure of social communication in rodents, ultrasonic vocalizations (USVs) in response to maternal separation are critical in preclinical research on neurodevelopmental disorders (NDDs). While sex differences in both USV production and behavioral outcomes are reported, many studies overlook sex as a biological variable in preclinical NDD models. We aimed to evaluate sex differences in USV call parameters and determine if USVs are differently impacted based on sex in the preclinical maternal immune activation (MIA) model.
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