The Evolution of Greater Humoral Immunity in Females Than Males: Implications for Vaccine Efficacy

Overview

Journal Curr Opin Physiol

Date 2018 Oct 16

PMID 30320243

Citations 77

Authors

Ashley L Fink

Sabra L Klein

Affiliations

Soon will be listed here.

Abstract

Males and females differ in their effector and memory immune responses to foreign and self-antigens. The difference in antibody responses (i.e., humoral immunity), in particular, is one of the most well conserved sex differences in immunology. Certain sex differences in humoral immunity are present throughout life, whereas others are only apparent after puberty and prior to reproductive senescence, suggesting that both genes and hormones are involved. Importantly, these sex-based differences in humoral immunity contribute to variation in the responses to vaccines and may explain some disparities in vaccine efficacy between the sexes. Elevated humoral immunity in females compared with males is phylogenetically well conserved, suggesting an adaptive advantage of elevated antibody for reproductive success, including for the transfer of protective antibodies to offspring.

Citing Articles

Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.

Peckham H, Radziszewska A, Sikora J, de Gruijter N, Restuadi R, Kartawinata M J Exp Med. 2025; 222(4).

PMID: 40049222 PMC: 11893172. DOI: 10.1084/jem.20241253.

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.

Evaluating the Adverse Effects and Associated Risk Factors of COVID-19 Vaccines Among Healthcare Workers: A Retrospective Study in the Duhok Province, Iraq.

Naqid I Cureus. 2024; 16(10):e71671.

PMID: 39553063 PMC: 11568403. DOI: 10.7759/cureus.71671.

Sex differences in response to COVID-19 mRNA vaccines in Italian population.

Ferroni E, Mateo-Urdiales A, Bietta C, Cesaroni G, Anticoli S, Di Maggio E Epidemiol Infect. 2024; 152:e139.

PMID: 39552125 PMC: 11574602. DOI: 10.1017/S0950268824001079.

Heterogeneity of the human immune response to malaria infection and vaccination driven by latent cytomegalovirus infection.

Mukhiya R, Fleischmann W, Loughland J, Chan J, De Labastida Rivera F, Andrew D EBioMedicine. 2024; 109:105419.

PMID: 39490199 PMC: 11576503. DOI: 10.1016/j.ebiom.2024.105419.

References

Zuk M . The sicker sex. PLoS Pathog. 2009; 5(1):e1000267. PMC: 2628977. DOI: 10.1371/journal.ppat.1000267. View

Vermeiren A, Hoebe C, Dukers-Muijrers N . High non-responsiveness of males and the elderly to standard hepatitis B vaccination among a large cohort of healthy employees. J Clin Virol. 2013; 58(1):262-4. DOI: 10.1016/j.jcv.2013.07.003. View

Vermillion M, Klein S . Pregnancy and infection: using disease pathogenesis to inform vaccine strategy. NPJ Vaccines. 2018; 3:6. PMC: 5794984. DOI: 10.1038/s41541-017-0042-4. 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

Kollmann T, Kampmann B, Mazmanian S, Marchant A, Levy O . Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity. 2017; 46(3):350-363. DOI: 10.1016/j.immuni.2017.03.009. View

Pap P, Czirjak G, Vagasi C, Barta Z, Hasselquist D . Sexual dimorphism in immune function changes during the annual cycle in house sparrows. Naturwissenschaften. 2010; 97(10):891-901. DOI: 10.1007/s00114-010-0706-7. 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

Nguyen D, Masseoud F, Lu X, Scinicariello F, Sambhara S, Attanasio R . 17β-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model. Vaccine. 2011; 29(14):2515-8. DOI: 10.1016/j.vaccine.2011.01.080. View

Martins C, Garly M, Bale C, Rodrigues A, Benn C, Whittle H . Measles antibody levels after vaccination with Edmonston-Zagreb and Schwarz measles vaccine at 9 months or at 9 and 18 months of age: a serological study within a randomised trial of different measles vaccines. Vaccine. 2013; 31(48):5766-71. DOI: 10.1016/j.vaccine.2013.08.044. View

10.

Pauklin S, Sernandez I, Bachmann G, Ramiro A, Petersen-Mahrt S . Estrogen directly activates AID transcription and function. J Exp Med. 2009; 206(1):99-111. PMC: 2626679. DOI: 10.1084/jem.20080521. View

11.

Marchbank K, Kulik L, Gipson M, Morgan B, Holers V . Expression of human complement receptor type 2 (CD21) in mice during early B cell development results in a reduction in mature B cells and hypogammaglobulinemia. J Immunol. 2002; 169(7):3526-35. DOI: 10.4049/jimmunol.169.7.3526. View

12.

Horstman A, Dillon E, Urban R, Sheffield-Moore M . The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci. 2012; 67(11):1140-52. PMC: 3636678. DOI: 10.1093/gerona/gls068. View

13.

Giglio T, Imro M, Filaci G, Scudeletti M, Puppo F, De Cecco L . Immune cell circulating subsets are affected by gonadal function. Life Sci. 1994; 54(18):1305-12. DOI: 10.1016/0024-3205(94)00508-7. View

14.

Simon A, Hollander G, McMichael A . Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015; 282(1821):20143085. PMC: 4707740. DOI: 10.1098/rspb.2014.3085. View

15.

Brandao A, de Oliveira T, Brandileone M, Goncalves J, Yara T, Simonsen V . Persistence of antibody response to pneumococcal capsular polysaccharides in vaccinated long term-care residents in Brazil. Vaccine. 2004; 23(6):762-8. DOI: 10.1016/j.vaccine.2004.07.024. View

16.

Hao Y, ONeill P, Naradikian M, Scholz J, Cancro M . A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood. 2011; 118(5):1294-304. PMC: 3152496. DOI: 10.1182/blood-2011-01-330530. View

17.

Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S . escapes X chromosome inactivation in immune cells. Sci Immunol. 2018; 3(19). DOI: 10.1126/sciimmunol.aap8855. View

18.

Lu F, Abel K, Ma Z, Rourke T, Lu D, Torten J . The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T cells under the influence of ovarian steroid hormones. Clin Exp Immunol. 2002; 128(1):10-20. PMC: 1906365. DOI: 10.1046/j.1365-2249.2002.01780.x. View

19.

Hirokawa K, Utsuyama M, Hayashi Y, Kitagawa M, Makinodan T, Fulop T . Slower immune system aging in women versus men in the Japanese population. Immun Ageing. 2013; 10(1):19. PMC: 3663722. DOI: 10.1186/1742-4933-10-19. View

20.

Marlovits S, Stocker R, Efstratiou A, Broughton K, Kaider A, Vecsei V . Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults. Eur J Clin Microbiol Infect Dis. 2000; 19(7):506-13. DOI: 10.1007/s100960000305. View