Sex-based Differences in Immune Function and Responses to Vaccination

Overview

Journal Trans R Soc Trop Med Hyg

Publisher Oxford University Press

Specialties Public Health
Tropical Medicine

Date 2015 Jan 10

PMID 25573105

Citations 280

Authors

Sabra L Klein

Ian Marriott

Eleanor N Fish

Affiliations

Soon will be listed here.

Abstract

Females typically develop higher antibody responses and experience more adverse reactions following vaccination than males. These differences are observed in response to diverse vaccines, including the bacillus Calmette-Guerin vaccine, the measles, mumps and rubella vaccine, the yellow fever virus vaccine and influenza vaccines. Sex differences in the responses to vaccines are observed across diverse age groups, ranging from infants to aged individuals. Biological as well as behavioral differences between the sexes are likely to contribute to differences in the outcome of vaccination between the sexes. Immunological, hormonal, genetic and microbiota differences between males and females may also affect the outcome of vaccination. Identifying ways to reduce adverse reactions in females and increase immune responses in males will be necessary to adequately protect both sexes against infectious diseases.

Citing Articles

Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy.

Yalcinkaya A, Yalcinkaya R, Sardh F, Landegren N Front Immunol. 2025; 15:1501364.

PMID: 39885993 PMC: 11779622. DOI: 10.3389/fimmu.2024.1501364.

MIP-3α-antigen fusion DNA vaccine enhances sex differences in tuberculosis model and alters dendritic cell activity early post vaccination.

Gordy J, Bates R, Glass E, Meza J, Li Y, Schill C Res Sq. 2025; .

PMID: 39877094 PMC: 11774437. DOI: 10.21203/rs.3.rs-5663995/v1.

Fast, Present and Future of the Concept of Spondyloarthritis.

Braun J Curr Rheumatol Rep. 2025; 27(1):15.

PMID: 39869233 DOI: 10.1007/s11926-024-01179-0.

Exploring How Adipose Tissue, Obesity, and Gender Influence the Immune Response to Vaccines: A Comprehensive Narrative Review.

De Sanctis J, Balda Noria G, Garcia A Int J Mol Sci. 2025; 26(2).

PMID: 39859575 PMC: 11765591. DOI: 10.3390/ijms26020862.

Molecular and Cellular Mechanisms of Immunosenescence: Modulation Through Interventions and Lifestyle Changes.

Pangrazzi L, Meryk A Biology (Basel). 2025; 14(1).

PMID: 39857248 PMC: 11760833. DOI: 10.3390/biology14010017.

References

Bean-Mayberry B, Yano E, Mor M, Bayliss N, Xu X, Fine M . Does sex influence immunization status for influenza and pneumonia in older veterans?. J Am Geriatr Soc. 2009; 57(8):1427-32. PMC: 2785130. DOI: 10.1111/j.1532-5415.2009.02316.x. View

Ferreira R, Antunes L, Finlay B . Should the human microbiome be considered when developing vaccines?. PLoS Pathog. 2010; 6(11):e1001190. PMC: 2987818. DOI: 10.1371/journal.ppat.1001190. View

Furman D, Hejblum B, Simon N, Jojic V, Dekker C, Thiebaut R . Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2013; 111(2):869-74. PMC: 3896147. DOI: 10.1073/pnas.1321060111. View

Roberts C, Walker W, Alexander J . Sex-associated hormones and immunity to protozoan parasites. Clin Microbiol Rev. 2001; 14(3):476-88. PMC: 88985. DOI: 10.1128/CMR.14.3.476-488.2001. View

Markle J, Frank D, Mortin-Toth S, Robertson C, Feazel L, Rolle-Kampczyk U . Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013; 339(6123):1084-8. DOI: 10.1126/science.1233521. View

Martineau A, White M, Bhopal R . No sex differences in immunisation rates of British south Asian children: the effect of migration?. BMJ. 1997; 314(7081):642-3. PMC: 2126092. DOI: 10.1136/bmj.314.7081.642. View

Lubahn D, Joseph D, Sullivan P, Willard H, French F, Wilson E . Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988; 240(4850):327-30. DOI: 10.1126/science.3353727. View

Asai K, Hiki N, Mimura Y, Ogawa T, Unou K, Kaminishi M . Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model. Shock. 2001; 16(5):340-3. DOI: 10.1097/00024382-200116050-00003. View

Amadori A, Zamarchi R, De Silvestro G, Forza G, Cavatton G, Danieli G . Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med. 1995; 1(12):1279-83. DOI: 10.1038/nm1295-1279. View

10.

Abramowitz L, Olivier-Van Stichelen S, Hanover J . Chromosome imbalance as a driver of sex disparity in disease. J Genomics. 2014; 2:77-88. PMC: 4091450. DOI: 10.7150/jgen.8123. View

11.

Opstelten W, van Essen G, Ballieux M, Goudswaard A . Influenza immunization of Dutch general practitioners: vaccination rate and attitudes towards vaccination. Vaccine. 2008; 26(47):5918-21. DOI: 10.1016/j.vaccine.2008.08.049. View

12.

Mitchell L . Sex differences in antibody- and cell-mediated immune response to rubella re-immunisation. J Med Microbiol. 1999; 48(12):1075-1080. DOI: 10.1099/00222615-48-12-1075. View

13.

Domingo C, Niedrig M . Safety of 17D derived yellow fever vaccines. Expert Opin Drug Saf. 2009; 8(2):211-21. DOI: 10.1517/14740330902808086. View

14.

Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C, Arnal J . The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling. Blood. 2011; 119(2):454-64. DOI: 10.1182/blood-2011-08-371831. View

15.

Bouman A, Heineman M, Faas M . Sex hormones and the immune response in humans. Hum Reprod Update. 2005; 11(4):411-23. DOI: 10.1093/humupd/dmi008. View

16.

Marriott I, Bost K, Huet-Hudson Y . Sexual dimorphism in expression of receptors for bacterial lipopolysaccharides in murine macrophages: a possible mechanism for gender-based differences in endotoxic shock susceptibility. J Reprod Immunol. 2006; 71(1):12-27. DOI: 10.1016/j.jri.2006.01.004. View

17.

Naik V, Kowli S, Solanki M, Gorey R, BHALERAO V . Exposition of the status of girl child in urban area. J Postgrad Med. 1991; 37(4):216-8. View

18.

Ailes E, Newsome K, Williams J, McIntyre A, Jamieson D, Finelli L . CDC Pregnancy Flu Line: monitoring severe illness among pregnant women with influenza. Matern Child Health J. 2013; 18(7):1578-82. PMC: 4498262. DOI: 10.1007/s10995-013-1415-6. View

19.

Khalil M, Al-Mazrou Y, Al-Ghamdi Y, Tumsah S, Al-Jeffri M, Meshkhas A . Effect of gender on reporting of MMR adverse events in Saudi Arabia. East Mediterr Health J. 2004; 9(1-2):152-8. View

20.

Benjamin C, Chew G, Silman A . Joint and limb symptoms in children after immunisation with measles, mumps, and rubella vaccine. BMJ. 1992; 304(6834):1075-8. PMC: 1881909. DOI: 10.1136/bmj.304.6834.1075. View