Toward an understanding of the immune responses that control infectious diseases

The vaccines against infectious diseases in use today are, with few exceptions, prepared from the causal agents themselves, either by inactivating them with a chemical such as formaldehyde or by attenuating them so that they grow and thus evoke an immune response in the natural host but cause no disease. These empirical approaches have produced many highly successful vaccines. Increasing knowledge at the molecular level of the agents and of the immune response to protein antigent is now providing us with the opportunity to design vaccines that will elicit protective responses without the need to use the agents themselves. The critical issue is to identify the immune responses that correlate with protection.

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Sex-Dependent Differences in Plasma Cytokine Responses to Hantavirus Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00035-08 ◽

2008 ◽

Vol 15 (5) ◽

pp. 885-887 ◽

Cited By ~ 32

Author(s):

Jonas Klingström ◽

Therese Lindgren ◽

Clas Ahlm

Keyword(s):

Sex Differences ◽

Infectious Diseases ◽

Immune Responses ◽

Infectious Agent ◽

Hantavirus Infection ◽

Infected Female ◽

Macrophage Colony Stimulating Factor ◽

Male Patients ◽

Macrophage Colony ◽

Interleukin 9

ABSTRACT There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.

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ON THE MECHANISM OF ALLOANTISERUM MEDIATED SUPPRESSION OF HISTOCOMPATIBILITY-LINKED Ir GENE CONTROLLED IMMUNE RESPONSES OF GUINEA PIGS**Supported by U.S.P.H.S. Research Grant Al 10931 from the National Institute of Allergy and Infectious Diseases.

Immune Recognition ◽

10.1016/b978-0-12-597850-7.50053-5 ◽

1975 ◽

pp. 651-665

Author(s):

Harry G. Bluestein

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Guinea Pigs ◽

Research Grant

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Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Cellular and Molecular Immunology ◽

10.1038/s41423-021-00754-0 ◽

2021 ◽

Vol 18 (10) ◽

pp. 2313-2324 ◽

Cited By ~ 1

Author(s):

Xin Wang ◽

Gang Xu ◽

Xiaoju Liu ◽

Yang Liu ◽

Shuye Zhang ◽

...

Keyword(s):

Risk Factors ◽

Severe Acute Respiratory Syndrome ◽

Infectious Diseases ◽

Immune Responses ◽

Single Cell ◽

Emerging Infectious Diseases ◽

Pathogenic Mechanisms ◽

Host Immune Responses ◽

Mechanistic Understanding

AbstractIn response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.

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Platelet Function in Viral Immunity and SARS-CoV-2 Infection

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1726033 ◽

2021 ◽

Author(s):

Afaf Allaoui ◽

Akif A. Khawaja ◽

Oussama Badad ◽

Mariam Naciri ◽

Marie Lordkipanidzé ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Infectious Diseases ◽

Immune Responses ◽

Cytokine Storm ◽

Blood Components ◽

Viral Immunity ◽

Cytokines And Chemokines ◽

Activated Platelets ◽

Viral Receptors

AbstractPlatelets, as nonnucleated blood components, are classically recognized for their pivotal role in hemostasis. In recent years, however, accumulating evidence points to a nonhemostatic role for platelets, as active participants in the inflammatory and immune responses to microbial organisms in infectious diseases. This stems from the ability of activated platelets to secrete a plethora of immunomodulatory cytokines and chemokines, as well as directly interplaying with viral receptors. While much attention has been given to the role of the cytokine storm in the severity of the coronavirus disease 2019 (COVID-19), less is known about the contribution of platelets to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we give a brief overview on the platelet contribution to antiviral immunity and response during SARS-CoV-2 infection.

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Editorial: The Role of Gene Polymorphisms in Modulating the Immune Responses Against Tropical Infectious Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2021.714237 ◽

2021 ◽

Vol 12 ◽

Author(s):

Adriana Malheiro ◽

Rajendranath Ramasawmy ◽

David Courtin ◽

Eduardo Antonio Donadi

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Gene Polymorphisms ◽

Tropical Infectious Diseases

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Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases

Frontiers in Pharmacology ◽

10.3389/fphar.2021.682286 ◽

2021 ◽

Vol 12 ◽

Author(s):

Seyed Davoud Jazayeri ◽

Hui Xuan Lim ◽

Kamyar Shameli ◽

Swee Keong Yeap ◽

Chit Laa Poh

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Vaccine Development ◽

Proteolytic Enzymes ◽

Oral Vaccine ◽

Oral Immunization ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Mucosal Surfaces ◽

Successful Vaccine

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

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The immunological impact of adenovirus early genes on vaccine-induced responses in mice and nonhuman primates

Journal of Virology ◽

10.1128/jvi.02253-20 ◽

2021 ◽

Author(s):

Kotou Sangare ◽

Iskra Tuero ◽

Mohammad Arif Rahman ◽

Tanya Hoang ◽

Leia K. Miller-Novak ◽

...

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Immune Responses ◽

Nonhuman Primates ◽

Clinical Use ◽

Early Region ◽

Early Genes ◽

Prevention And Treatment ◽

Infected Cells ◽

In Cells

Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Ad with a deletion in early region 3 (ΔE3) provokes a stronger immune response than Ad with deletions in early regions 1 and E3 (ΔE1/ΔE3). The ΔE1/ΔE3 Ads are more popular because they can carry a larger transgene and because of the deleted E1 (E1A and E1B), are perceived safer for clinical use. Ad with a deletion in E1B55K (ΔE1B55K) has been in phase III clinical trials for use in cancer therapy in the US and has been approved for use in head and neck tumor therapy in China, demonstrating that Ad containing E1A are safe for clinical use. We have shown previously that ΔE1B55K Ad, even while promoting lower levels of an inserted transgene, promoted similar levels of transgene-specific immune responses as a ΔE3 Ad. Products of the Ad early region 4 (E4) limit the ability of cells to mount an innate immune response. Using this knowledge, we deleted the Ad E4 open reading frames 1-4 (E4orf1-4) from the ΔE1B55K Ad. Here, we show that innate cytokine network genes are elevated in the ΔE4 Ad-infected cells beyond that of ΔE3 Ad-infected cells. Further, in immunized mice the IgG2a subclass was favored as was the IgG1 subclass in immunized nonhuman primates. Thus, Ad E4 impacts immune responses in cells, in immunized mice, and immunized nonhuman primates. These Ad may offer advantages that are beneficial for clinical use. Importance: Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Here we provide evidence in cells, mice, and nonhuman primates supporting the notion that Ad early gene-products limit specific immune responses. Ad constructed with deletions in early genes and expressing HIV envelope protein was shown to induce greater HIV-specific cellular immune responses and higher titer antibodies compared to the parental Ad with the early genes. In addition to eliciting enhanced immunity, the deleted Ad possesses more space for insertion of additional or larger transgenes needed for targeting other infectious agents or cancers.

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Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa450 ◽

2020 ◽

Vol 7 (11) ◽

Author(s):

Guillaume Butler-Laporte ◽

Devin Kreuzer ◽

Tomoko Nakanishi ◽

Adil Harroud ◽

Vincenzo Forgetta ◽

...

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Vaccine Development ◽

Association Studies ◽

Case Control ◽

Genome Wide Association Studies ◽

Genetic Determinants ◽

Hla Association ◽

Genome Wide ◽

A Genome

Abstract Background Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development. Methods We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 seropositivity case–control phenotypes and 31 quantitative antibody measurement phenotypes. For each of these, we performed genome-wide association studies (GWAS) using the fastGWA linear mixed model package and human leukocyte antigen (HLA) classical allele and amino acid residue associations analyses using Lasso regression for variable selection. Results We included a total of 8735 individuals for case–control phenotypes, and an average (range) of 4286 (276–8555) samples per quantitative analysis. Fourteen of the GWAS yielded a genome-wide significant (P < 5 ×10-8) locus at the major histocompatibility complex (MHC) on chromosome 6. Outside the MHC, we found a total of 60 loci, multiple associated with Epstein-Barr virus (EBV)–related NCDs (eg, RASA3, MED12L, and IRF4). FUT2 was also identified as an important gene for polyomaviridae. HLA analysis highlighted the importance of DRB1*09:01, DQB1*02:01, DQA1*01:02, and DQA1*03:01 in EBV serologies and of DRB1*15:01 in polyomaviridae. Conclusions We have identified multiple genetic variants associated with antibody immune response to 13 infections, many of which are biologically plausible therapeutic or vaccine targets. This may help prioritize future research and drug development.

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