Sex differences in immune responses to vaccines

A few studies have shown that male and female invertebrates differ in immunity and that these differences appear related to differences in sexual dimorphism and gender differences in life histories. Melanotic encapsulation of foreign objects in insects is one form of immunity. The damselfly Lestes forcipatus Rambur is moderately sexually dimorphic, and much is known about patterns of mass gain in congeners relating to differences in life history between males and females. In this study, females were more immunoresponsive than males under controlled temperatures, following emergence, and at a time when parasitic mites were challenging these hosts. However, males and females that overlapped in mass at emergence did not differ in their immune responses. Males in better condition at emergence were more immunoresponsive than lighter males, but this relation was not found in females. Sex differences in immune expression may have implications for how females versus males are able to deal with challenges from parasites, under varying environmental conditions.

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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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Sex differences in the temporal development of pronociceptive immune responses in the tibia fracture mouse model

Pain ◽

10.1097/j.pain.0000000000001592 ◽

2019 ◽

Vol 160 (9) ◽

pp. 2013-2027 ◽

Cited By ~ 2

Author(s):

Tian-Zhi Guo ◽

Xiaoyou Shi ◽

Wen-Wu Li ◽

Tzuping Wei ◽

J. David Clark ◽

...

Keyword(s):

Sex Differences ◽

Mouse Model ◽

Immune Responses ◽

Tibia Fracture ◽

Temporal Development

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Sex differences in T cell immune responses, gut permeability and outcome after ischemic stroke in aged mice

Brain Behavior and Immunity ◽

10.1016/j.bbi.2020.02.001 ◽

2020 ◽

Vol 87 ◽

pp. 556-567 ◽

Cited By ~ 5

Author(s):

Hilda Ahnstedt ◽

Anthony Patrizz ◽

Anjali Chauhan ◽

Meaghan Roy-O'Reilly ◽

Joseph W. Furr ◽

...

Keyword(s):

Sex Differences ◽

Ischemic Stroke ◽

T Cell ◽

Immune Responses ◽

Gut Permeability ◽

Aged Mice ◽

T Cell Immune Responses

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Cutting Edge: CXCR3 Escapes X Chromosome Inactivation in T Cells during Infection: Potential Implications for Sex Differences in Immune Responses

The Journal of Immunology ◽

10.4049/jimmunol.1800931 ◽

2019 ◽

Vol 203 (4) ◽

pp. 789-794 ◽

Cited By ~ 8

Author(s):

Steve Oghumu ◽

Sanjay Varikuti ◽

James C. Stock ◽

Greta Volpedo ◽

Noushin Saljoughian ◽

...

Keyword(s):

T Cells ◽

Sex Differences ◽

Immune Responses ◽

X Chromosome ◽

X Chromosome Inactivation ◽

Cutting Edge ◽

Chromosome Inactivation

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Sex differences in severity and mortality from COVID-19: are males more vulnerable?

Biology of Sex Differences ◽

10.1186/s13293-020-00330-7 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Ajay Pradhan ◽

Per-Erik Olsson

Keyword(s):

Sex Differences ◽

Immune System ◽

Immune Responses ◽

Molecular Mechanisms ◽

Viral Infections ◽

Basic Research ◽

Contributing Factors ◽

High Infection ◽

Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

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An overview of sex hormones in relation to SARS-CoV-2 infection

Future Virology ◽

10.2217/fvl-2021-0058 ◽

2021 ◽

Author(s):

Marzieh Saei Ghare Naz ◽

Mojdeh Banaei ◽

Sareh Dashti ◽

Fahimeh Ramezani Tehrani

Keyword(s):

Sex Differences ◽

Immune System ◽

Literature Review ◽

Immune Responses ◽

Sex Hormones ◽

Web Of Science ◽

Vaccine Development ◽

Response To Treatment ◽

Different Seasons ◽

Body Response

Aim: Sex differences in COVID-19 outcomes might be explained from a sex hormones (SexHs) perspective. Materials & methods: PubMed, Scopus, Web of Science, EMBASE and Google Scholar were searched up to March 2021. Results: Based on the literature review, the crosstalk between SexHs (estrogens, progesterone and testosterone), their receptors (estrogen α and β, androgen, and progesterone) and the immune system shaped the sex-related differences in immune responses against COVID-19. Differential production of SexHs over the lifespan (during pregnancy, reproductive years, menopause and andropause) and over different seasons may result in disparities in body response toward COVID-19. Moreover, SexHs-specific differences might affect vaccine efficacy and response to treatment. Conclusion: The roles of SexHs need to be considered in vaccine development and even treatment of COVID-19.

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Sex differences in concentrations of HMGB1 and numbers of pigmented monocytes in infants with malaria

10.1101/2021.03.26.437109 ◽

2021 ◽

Author(s):

Bernard N. Kanoi ◽

Thomas G. Egwang

Keyword(s):

Sex Differences ◽

Immune Responses ◽

Clinical Malaria ◽

Northern Uganda ◽

Asymptomatic Malaria ◽

Serum Concentrations ◽

Endemic Region ◽

Adaptive Immune ◽

Cytokines And Chemokines ◽

Malaria Endemic Region

Females generally mount more robust innate and adaptive immune responses and demonstrate a higher rate of morbidity, and prevalence of autoimmune diseases by comparison with males. In malaria, females demonstrate higher concentrations of antibodies and rates of severe adverse events and mortality following natural infections and malaria vaccination. Although monocytes/macrophages play a crucial role in disease and protection in malaria, no studies have investigated sex differences in their functions in production of proinflammatory cytokines and chemokines in malaria-infected subjects. Here, we show significant sex differences in serum concentrations of HMGB1, a non-histone chromatin-associated protein, and numbers of pigmented monocytes, which are both markers of severe malaria, in infants <5 years old from a malaria endemic region in Northern Uganda. Female infants with clinical malaria had significantly higher HMGB1 concentrations than male infants, and female infants with asymptomatic malaria had significantly lower numbers of pigmented monocytes than male infants with asymptomatic malaria. There was (1) a significant correlation between HMGB1 concentrations and pigmented monocyte numbers in female but not male infants; and (2) a significant correlation between HMGB1 concentrations and parasite densities in female but not male infants. These findings suggest that female infants with clinical malaria might be at a greater risk of morbidity characterized by higher serum HMGB1 levels.

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Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study

Scientific Reports ◽

10.1038/s41598-021-03044-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eteri Regis ◽

Sara Fontanella ◽

Lijing Lin ◽

Rebecca Howard ◽

Sadia Haider ◽

...

Keyword(s):

Sex Differences ◽

Immune Responses ◽

Birth Cohort ◽

Respiratory Virus ◽

Respiratory Infections ◽

Respiratory Viruses ◽

Innate Immune ◽

Innate Immune Responses ◽

Virus Infections ◽

Respiratory Virus Infections

AbstractThe mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 − < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

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