Both sex (i.e., biological differences) and gender (i.e., social or cultural influences) impact vaccine acceptance, responses, and outcomes. Clinical data illustrate that among children, young adults, and aged individuals, males and females differ in vaccine-induced immune responses, adverse events, and protection. Although males are more likely to receive vaccines, following vaccination, females typically develop higher antibody responses and report more adverse effects of vaccination than do males. Human, nonhuman animal, and in vitro studies reveal numerous immunological, genetic, hormonal, and environmental factors that differ between males and females and contribute to sex- and gender-specific vaccine responses and outcomes. Herein, we address the impact of sex and gender variables that should be considered in preclinical and clinical studies of vaccines.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Aaby P, Benn CS, Neilsen J, Lisse IM, Rodrigues A, Ravn H. 2012. Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries. BMJ Open 2:e000707 [Google Scholar]
  2. Aaby P, Garly ML, Nielsen J, Ravn H, Martins C. et al. 2007. Increased female-male mortality ratio associated with inactivated polio and diphtheria-tetanus-pertussis vaccines: observations from vaccination trials in Guinea-Bissau. Pediatr. Infect. Dis. J. 26:247–52 [Google Scholar]
  3. Aaby P, Jensen H, Samb B, Cisse B, Sodemann M. et al. 2003. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies. Lancet 361:2183–88 [Google Scholar]
  4. Aaby P, Kollmann TR, Benn CS. 2014. Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges. Nat. Immunol. 15:895–99 [Google Scholar]
  5. Aaby P, Martins C, Bale C, Garly ML, Rodrigues A. et al. 2010. Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-Bissau. Pediatr. Infect. Dis. J. 29:324–28 [Google Scholar]
  6. Aaby P, Ravn H, Benn CS. 2016a. The WHO review of the possible nonspecific effects of diphtheria-tetanus-pertussis vaccine. Pediatr. Infect. Dis. J. 35:1247–57 [Google Scholar]
  7. Aaby P, Ravn H, Fisker AB, Rodrigues A, Benn CS. 2016b. Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine. Trans. R. Soc. Trop. Med. Hyg 110:570–81 [Google Scholar]
  8. Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A. et al. 2011. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period. J. Infect. Dis. 204:245–52 [Google Scholar]
  9. Abdi F, Mobedi H, Mosaffa N, Dolatian M, Ramezani Tehrani F. 2016. Effects of hormone replacement therapy on immunological factors in the postmenopausal period. Climacteric 19:234–39 [Google Scholar]
  10. Abdullah M, Chai PS, Chong MY, Tohit ER, Ramasamy R. et al. 2012. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol 272:214–19 [Google Scholar]
  11. Altet MN, Alcaide J, Canela J, Serra L, Salleras L. 1992. Retrospective evaluation of the effectiveness of the BCG vaccine campaign in newborns of Barcelona. Med. Clin 99:612–16 [Google Scholar]
  12. Atarashi K, Honda K. 2011. Microbiota in autoimmunity and tolerance. Curr. Opin. Immunol. 23:761–68 [Google Scholar]
  13. Bayas J, Vilella A, Bertran M, Vidal J, Batalla J. et al. 2001. Immunogenicity and reactogenicity of the adult tetanus–diphtheria vaccine. How many doses are necessary. Epidemiol. Infect. 127:451–60 [Google Scholar]
  14. Baynam G, Zhang G, Khoo SK, Sly P, Holt P. et al. 2008. Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses. Vaccine 26:3574–79 [Google Scholar]
  15. Bejon P, White MT, Olotu A, Bojang K, Lusingu JP. et al. 2013. Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data. Lancet Infect. Dis. 13:319–27 [Google Scholar]
  16. Bocsan IS, Gocan G, Ursu L, Brumboiu MI, Sosa I. et al. 2005. How protective is the immunization against viral hepatitis B prospectively? Seroprevalence study on viral hepatitis B infection. Rev. Med. Chir. Soc. Med. Nat. Iasi 109:124–30 [Google Scholar]
  17. Bodeker B, Betsch C, Wichmann O. 2015. Skewed risk perceptions in pregnant women: the case of influenza vaccination. BMC Public Health 16:1308 [Google Scholar]
  18. Bolnick DI, Snowberg LK, Hirsch PE, Lauber CL, Org E. et al. 2014. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nat. Commun. 5:4500 [Google Scholar]
  19. Booy R, Khandaker G, Heron LG, Yin J, Doyle B. et al. 2011. Cross-reacting antibodies against the pandemic (H1N1) 2009 influenza virus in older Australians. Med. J. Aust. 194:19 [Google Scholar]
  20. Brandão AP, de Oliveira TC, de Cunto Brandileone MC, Gonçalves JE, Yara TI, Simonsen V. 2004. Persistence of antibody response to pneumococcal capsular polysaccharides in vaccinated long term-care residents in Brazil. Vaccine 23:762–68 [Google Scholar]
  21. Bruckner S, Agnandji ST, Berberich S, Bache E, Fernandes JF. et al. 2015. Effect of antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine in primary school children in Gabon: a randomized placebo-controlled trial. PLOS Negl. Trop. Dis. 9:e0003768 [Google Scholar]
  22. Burl S, Adetifa UJ, Cox M, Touray E, Whittle H. et al. 2010. The tuberculin skin test (TST) is affected by recent BCG vaccination but not by exposure to non-tuberculosis mycobacteria (NTM) during early life. PLOS ONE 5:e12287 [Google Scholar]
  23. Burl S, Townend J, Njie-Jobe J, Cox M, Adetifa UJ. et al. 2011. Age-dependent maturation of Toll-like receptor-mediated cytokine responses in Gambian infants. PLOS ONE 6:e18185 [Google Scholar]
  24. Case LK, Toussaint L, Moussawi M, Roberts B, Saligrama N. et al. 2012. Chromosome Y regulates survival following murine coxsackievirus B3 infection. G3 2:115–21 [Google Scholar]
  25. Castellsague X, Giuliano AR, Goldstone S, Guevara A, Mogensen O. et al. 2015. Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine 33:6892–901 [Google Scholar]
  26. Cerf-Bensussan N, Gaboriau-Routhiau V. 2010. The immune system and the gut microbiota: friends or foes?. Nat. Rev. Immunol. 10:735–44 [Google Scholar]
  27. Cernetich A, Garver LS, Jedlicka AE, Klein PW, Kumar N. et al. 2006. Involvement of gonadal steroids and gamma interferon in sex differences in response to blood-stage malaria infection. Infect. Immun. 74:3190–203 [Google Scholar]
  28. Chamberlain AT, Seib K, Ault KA, Orenstein WA, Frew PM. et al. 2015. Factors associated with intention to receive influenza and tetanus, diphtheria, and acellular pertussis (Tdap) vaccines during pregnancy: a focus on vaccine hesitancy and perceptions of disease severity and vaccine safety. PLOS Curr. Outbreaks. https://doi.org/10.1371/currents.outbreaks.d37b61bceebae5a7a06d40a301cfa819 [Crossref]
  29. Chang S, Ball R, Braun MM. 2008. Elective termination of pregnancy after vaccination reported to the Vaccine Adverse Event Reporting System (VAERS): 1990–2006. Vaccine 26:2428–32 [Google Scholar]
  30. Cook IF. 2008. Sexual dimorphism of humoral immunity with human vaccines. Vaccine 26:3551–55 [Google Scholar]
  31. Cook IF. 2009. Sex differences in injection site reactions with human vaccines. Hum. Vaccines 5:441–49 [Google Scholar]
  32. Cook IF, Pond D, Hartel G. 2007. Comparative reactogenicity and immunogenicity of 23 valent pneumococcal vaccine administered by intramuscular or subcutaneous injection in elderly adults. Vaccine 25:4767–74 [Google Scholar]
  33. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA. 2012. The application of ecological theory toward an understanding of the human microbiome. Science 336:1255–62 [Google Scholar]
  34. Dai R, McReynolds S, Leroith T, Heid B, Liang Z, Ahmed SA. 2013. Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol. Sex Differ. 4:19 [Google Scholar]
  35. Daniel-Ulloa J, Gilbert PA, Parker EA. 2016. Human papillomavirus vaccination in the United States: uneven uptake by gender, race/ethnicity, and sexual orientation. Am. J. Public Health 106:746–7 [Google Scholar]
  36. Dannecker G, Mecheri S, Heuser M, Ihle J, Hoffmann MK, Niethammer D. 1993. Differential expression of T cell receptor variable beta genes on CD4+ and CD8+ T cells: influence by sex linked genes?. Immunobiology 187:17–23 [Google Scholar]
  37. Di Benedetto S, Derhovanessian E, Steinhagen-Thiessen E, Goldeck D, Muller L, Pawelec G. 2015. Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study. Biogerontology 16:631–43 [Google Scholar]
  38. Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L. et al. 2015. Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLOS ONE 10:e0124599 [Google Scholar]
  39. Engler RJ, Nelson MR, Klote MM, VanRaden MJ, Huang CY. et al. 2008. Half-versus full-dose trivalent inactivated influenza vaccine (2004–2005): age, dose, and sex effects on immune responses. Arch. Intern. Med. 168:2405–14 [Google Scholar]
  40. Fan H, Dong G, Zhao G, Liu F, Yao G. et al. 2014. Gender differences of B cell signature in healthy subjects underlie disparities in incidence and course of SLE related to estrogen. J. Immunol. Res 2014:814598 [Google Scholar]
  41. Fink AL, Klein SL. 2015. Sex and gender impact immune responses to vaccines among the elderly. Physiology 30:408–16 [Google Scholar]
  42. Flanagan KL, Jensen KJ. 2015. Sex differences in outcomes of infections and vaccinations in under five-year-old children. Sex and Gender Differences in Infection and Treatments for Infectious Diseases SL Klein, CW Roberts 273–312 Cham, Switz.: Springer Int [Google Scholar]
  43. Flanagan KL, Plebanski M. 2017. Sex-differential heterologous (non-specific) effects of vaccines: an emerging public health issue that needs to be understood and exploited. Expert Rev. Vaccines 16:5–13 [Google Scholar]
  44. Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O. 2013. Heterologous (“nonspecific”) and sex-differential effects of vaccines: epidemiology, clinical trials, and emerging immunologic mechanisms. Clin. Infect. Dis. 57:283–89 [Google Scholar]
  45. Fleming D, Watson J, Nicholas S, Smith G, Swan A. 1995. Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989–90 using a general practice database. Epidemiol. Infect. 115:581–89 [Google Scholar]
  46. Fox HS, Bond BL, Parslow TG. 1991. Estrogen regulates the IFN-gamma promoter. J. Immunol. 146:4362–67 [Google Scholar]
  47. France EK, Glanz J, Xu S, Hambidge S, Yamasaki K. et al. 2008. Risk of immune thrombocytopenic purpura after measles-mumps-rubella immunization in children. Pediatrics 121:e687–92 [Google Scholar]
  48. Freire AC, Basit AW, Choudhary R, Piong CW, Merchant HA. 2011. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. Int. J. Pharm. 415:15–28 [Google Scholar]
  49. Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL. et al. 2014. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. PNAS 111:869–74 [Google Scholar]
  50. Gameiro C, Romao F. 2010. Changes in the immune system during menopause and aging. Front. Biosci. 2:1299–303 [Google Scholar]
  51. Garly ML, Jensen H, Martins CL, Bale C, Balde MA. et al. 2004. Hepatitis B vaccination associated with higher female than male mortality in Guinea-Bissau: an observational study. Pediatr. Infect. Dis. J. 23:1086–92 [Google Scholar]
  52. Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. 1995. A population-based serologic survey of immunity to tetanus in the United States. N. Engl. J. Med. 332:761–67 [Google Scholar]
  53. Geurs TL, Hill EB, Lippold DM, French AR. 2012. Sex differences in murine susceptibility to systemic viral infections. J. Autoimmun. 38:J245–53 [Google Scholar]
  54. Ghorai A, Ghosh U. 2014. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or post-transcriptional processing of coding genes. Front. Genet. 5:100 [Google Scholar]
  55. Giefing-Kröll C, Berger P, Lepperdinger G, Grubeck‐Loebenstein B. 2015. How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14:309–21 [Google Scholar]
  56. Goetzl EJ, Huang MC, Kon J, Patel K, Schwartz JB. et al. 2010. Gender specificity of altered human immune cytokine profiles in aging. FASEB J 24:3580–89 [Google Scholar]
  57. Goldblatt D, Southern J, Andrews N, Ashton L, Burbidge P. et al. 2009. The immunogenicity of 7-valent pneumococcal conjugate vaccine versus 23-valent polysaccharide vaccine in adults aged 50–80 years. Clin. Infect. Dis. 49:1318–25 [Google Scholar]
  58. Hainz U, Jenewein B, Asch E, Pfeiffer K-P, Berger P, Grubeck-Loebenstein B. 2005. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine 23:3232–35 [Google Scholar]
  59. Haq K, Fulop T, Tedder G, Gentleman B, Garneau H. et al. 2016. Cytomegalovirus seropositivity predicts a decline in the T cell but not the antibody response to influenza in vaccinated older adults independent of type 2 diabetes status. J. Gerontol. A Biol. Sci. Med. Sci. https://doi.org/10.1093/gerona/glw216 [Crossref] [Google Scholar]
  60. Haq K, McElhaney JE. 2014. Immunosenescence: influenza vaccination and the elderly. Curr. Opin. Immunol. 29:38–42 [Google Scholar]
  61. Haralambieva IH, Ovsyannikova IG, Kennedy RB, Larrabee BR, Shane Pankratz V, Poland GA. 2013. Race and sex-based differences in cytokine immune responses to smallpox vaccine in healthy individuals. Hum. Immunol. 74:1263–66 [Google Scholar]
  62. Harris VC, Armah G, Fuentes S, Korpela KE, Parashar U. et al. 2017. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana. J. Infect. Dis. 215:34–41 [Google Scholar]
  63. Haselow D. 2016. Vaccination-related side effects, humoral immunity, and adverse events during the civilian smallpox vaccination campaign, Arkansas, 2003. Public Health Nurs 33:129–38 [Google Scholar]
  64. Hewagama A, Patel D, Yarlagadda S, Strickland FM, Richardson BC. 2009. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes Immun 10:509–16 [Google Scholar]
  65. Higgins JP, Soares-Weiser K, Lopez-Lopez JA, Kakourou A, Chaplin K. et al. 2016. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 355:i5170 [Google Scholar]
  66. Hillebrand K, Bricout H, Schulze-Rath R, Schink T, Garbe E. 2015. Incidence of herpes zoster and its complications in Germany, 2005–2009. J. Infect. 70:178–86 [Google Scholar]
  67. Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ. et al. 2015. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar. J. 14:381 [Google Scholar]
  68. Ivanov II, Honda K. 2012. Intestinal commensal microbes as immune modulators. Cell Host Microbe 12:496–508 [Google Scholar]
  69. Jackowska T, Dziadek J, Wasilewski R, Wasik M. 2008. Safety and efficacy of varicella vaccine in healthy children—one year follow-up. Med. Wieku Rozwojowego 12:653–59 [Google Scholar]
  70. Jensen KJ, Larsen N, Biering-Sorensen S, Andersen A, Eriksen HB. et al. 2015a. Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial. J. Infect. Dis. 211:956–67 [Google Scholar]
  71. Jensen KJ, Ndure J, Plebanski M, Flanagan KL. 2015b. Heterologous and sex differential effects of administering vitamin A supplementation with vaccines. Trans. R. Soc. Trop. Med. Hyg 109:36–45 [Google Scholar]
  72. Jensen KJ, Sondergaard M, Andersen A, Sartono E, Martins C. et al. 2014. A randomized trial of an early measles vaccine at 41/2 months of age in Guinea-Bissau: sex-differential immunological effects. PLOS ONE 9:e97536 [Google Scholar]
  73. Jentsch-Ullrich K, Koenigsmann M, Mohren M, Franke A. 2005. Lymphocyte subsets' reference ranges in an age- and gender-balanced population of 100 healthy adults—a monocentric German study. Clin. Immunol. 116:192–97 [Google Scholar]
  74. Kallikourdis M, Betz AG. 2007. Periodic accumulation of regulatory T cells in the uterus: preparation for the implantation of a semi-allogeneic fetus?. PLOS ONE 2:e382 [Google Scholar]
  75. Kao TM, Hsieh SM, Kung HC, Lee YC, Huang KC. et al. 2010. Immune response of single dose vaccination against 2009 pandemic influenza A (H1N1) in the Taiwanese elderly. Vaccine 28:6159–63 [Google Scholar]
  76. Karunasena E, McMahon KW, Chang D, Brashears MM. 2014. Host responses to the pathogen Mycobacterium avium subsp. paratuberculosis and beneficial microbes exhibit host sex specificity. Appl. Environ. Microbiol 80:4481–90 [Google Scholar]
  77. Kawai K, Msamanga G, Manji K, Villamor E, Bosch RJ. et al. 2010. Sex differences in the effects of maternal vitamin supplements on mortality and morbidity among children born to HIV-infected women in Tanzania. Br. J. Nutr. 103:1784–91 [Google Scholar]
  78. Kesteman T, Randrianarivelojosia M, Mattern C, Raboanary E, Pourette D. et al. 2014. Nationwide evaluation of malaria infections, morbidity, mortality, and coverage of malaria control interventions in Madagascar. Malar. J. 13:465 [Google Scholar]
  79. Khalil MK, Al-Mazrou YY, Al-Ghamdi YS, Tumsah S, Al-Jeffri M, Meshkhas A. 2003. Effect of gender on reporting of MMR adverse events in Saudi Arabia. East Mediterr. Health J. 9:152–58 [Google Scholar]
  80. Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S. et al. 2012. Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum. Mol. Genet. 21:2086–101 [Google Scholar]
  81. Khurana S, Verma N, Talaat KR, Karron RA, Golding H. 2012. Immune response following H1N1pdm09 vaccination: differences in antibody repertoire and avidity in young adults and elderly populations stratified by age and gender. J. Infect. Dis. 205:610–20 [Google Scholar]
  82. Kitaura K, Kanayama K, Fujii Y, Shiobara N, Tanaka K. et al. 2009. T cell receptor repertoire in BALB/c mice varies according to tissue type, sex, age, and hydrocortisone treatment. Exp. Anim. 58:159–68 [Google Scholar]
  83. Klein SL. 2004. Hormonal and immunological mechanisms mediating sex differences in parasite infection. Parasite Immunol 26:247–64 [Google Scholar]
  84. Klein SL, Flanagan KL. 2016. Sex differences in immune responses. Nat. Rev. Immunol. 16:626–38 [Google Scholar]
  85. Klein SL, Jedlicka A, Pekosz A. 2010. The Xs and Y of immune responses to viral vaccines. Lancet Infect. Dis. 10:338–49 [Google Scholar]
  86. Klein SL, Marriott I, Fish EN. 2015. Sex-based differences in immune function and responses to vaccination. Trans. R. Soc. Trop. Med. Hyg 109:9–15 [Google Scholar]
  87. Klein SL, Pekosz A. 2014. Sex-based biology and the rational design of influenza vaccination strategies. J. Infect. Dis. 209:Suppl. 3114–19 [Google Scholar]
  88. Klein SL, Shann F, Moss WJ, Benn CS, Aaby P. 2016. RTS,S malaria vaccine and increased mortality in girls. mBio 7:e00514–16 [Google Scholar]
  89. Klett-Tammen CJ, Krause G, Seefeld L, Ott JJ. 2016. Determinants of tetanus, pneumococcal and influenza vaccination in the elderly: a representative cross-sectional study on knowledge, attitude and practice (KAP). BMC Public Health 16:121 [Google Scholar]
  90. Knudsen KM, Aaby P, Whittle H, Rowe M, Samb B. et al. 1996. Child mortality following standard, medium or high titre measles immunization in West Africa. Int. J. Epidemiol. 25:665–73 [Google Scholar]
  91. Kollmann TR, Levy O, Montgomery RR, Goriely S. 2012. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37:771–83 [Google Scholar]
  92. Kovats S. 2015. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol 294:63–69 [Google Scholar]
  93. Kovats S, Carreras E, Agrawal H. 2010. Sex steroid receptors in immune cells. Sex Hormones and Immunity to Infection SL Klein, CW Roberts 53–92 Berlin: Springer-Verlag [Google Scholar]
  94. Kumru S, Godekmerdan A, Yilmaz B. 2004. Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women. J. Reprod. Immunol. 63:31–38 [Google Scholar]
  95. Levy O, Coughlin M, Cronstein BN, Roy RM, Desai A, Wessels MR. 2006. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J. Immunol. 177:1956–66 [Google Scholar]
  96. Li J. 2004. Gender inequality, family planning, and maternal and child care in a rural Chinese county. Soc. Sci. Med. 59:695–708 [Google Scholar]
  97. Li M, Wang B, Zhang M, Rantalainen M, Wang S. et al. 2008. Symbiotic gut microbes modulate human metabolic phenotypes. PNAS 105:2117–22 [Google Scholar]
  98. Libert C, Dejager L, Pinheiro I. 2010. The X chromosome in immune functions: when a chromosome makes the difference. Nat. Rev. Immunol. 10:594–604 [Google Scholar]
  99. Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF. et al. 2008. Adverse event reports following yellow fever vaccination. Vaccine 26:6077–82 [Google Scholar]
  100. Livingston BD, Alexander J, Crimi C, Oseroff C, Celis E. et al. 1999. Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans. J. Immunol. 162:3088–95 [Google Scholar]
  101. Lorenzo ME, Hodgson A, Robinson DP, Kaplan JB, Pekosz A, Klein SL. 2011. Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. Vaccine 29:9246–55 [Google Scholar]
  102. Lu FX, Abel K, Ma Z, Rourke T, Lu D. et al. 2002. 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. 128:10–20 [Google Scholar]
  103. Maizels RM, McSorley HJ. 2016. Regulation of the host immune system by helminth parasites. J. Allergy Clin. Immunol. 138:666–75 [Google Scholar]
  104. Malhotra I, McKibben M, Mungai P, McKibben E, Wang X. et al. 2015. Effect of antenatal parasitic infections on anti-vaccine IgG levels in children: a prospective birth cohort study in Kenya. PLOS Negl. Trop. Dis. 9:e0003466 [Google Scholar]
  105. Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM. et al. 2013. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339:1084–88 [Google Scholar]
  106. Marlovits S, Stocker R, Efstratiou A, Broughton K, Kaider A. et al. 2000. Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults. Eur. J. Clin. Microbiol. Infect. Dis. 19:506–13 [Google Scholar]
  107. Martins S, Livramento A, Andrigueti M, Kretzer IF, Machado MJ. et al. 2014. The prevalence of hepatitis B virus infection markers and socio-demographic risk factors in HIV-infected patients in Southern Brazil. Rev. Soc. Bras. Med. Trop 47:552–58 [Google Scholar]
  108. Merten S, Martin Hilber A, Biaggi C, Secula F, Bosch-Capblanch X. et al. 2015. Gender determinants of vaccination status in children: evidence from a meta-ethnographic systematic review. PLOS ONE 10:e0135222 [Google Scholar]
  109. Mesch GS, Schwirian KP. 2015. Social and political determinants of vaccine hesitancy: Lessons learned from the H1N1 pandemic of 2009–2010. Am. J. Infect. Control 43:1161–65 [Google Scholar]
  110. Mitchell LA. 1999. Sex differences in antibody- and cell-mediated immune response to rubella re-immunisation. J. Med. Microbiol 48:1075–80 [Google Scholar]
  111. Motta-Castro AR, Gomes SA, Yoshida CF, Miguel JC, Teles SA, Martins RM. 2009. Compliance with and response to hepatitis B vaccination in remaining quilombo communities in Central Brazil. Cad. Saúde Publica 25:738–42 [Google Scholar]
  112. Mueller S, Saunier K, Hanisch C, Norin E, Alm L. et al. 2006. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl. Environ. Microbiol. 72:1027–33 [Google Scholar]
  113. Narayanan PR. 2006. Influence of sex, age & nontuberculous infection at intake on the efficacy of BCG: re-analysis of 15-year data from a double-blind randomized control trial in South India. Indian J. Med. Res 123:119–24 [Google Scholar]
  114. Ndure J, Flanagan KL. 2014. Targeting regulatory T cells to improve vaccine immunogenicity in early life. Front. Microbiol. 5:477 [Google Scholar]
  115. Nguyen DC, Masseoud F, Lu X, Scinicariello F, Sambhara S, Attanasio R. 2011. 17β-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model. Vaccine 29:2515–18 [Google Scholar]
  116. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. 2007. Effectiveness of influenza vaccine in the community-dwelling elderly. N. Engl. J. Med. 357:1373–81 [Google Scholar]
  117. Noho-Konteh F, Adetifa JU, Cox M, Hossin S, Reynolds J. et al. 2016. Sex-differential non-vaccine-specific immunological effects of diphtheria-tetanus-pertussis and measles vaccination. Clin. Infect. Dis. 63:1213–26 [Google Scholar]
  118. Noland GS, Chowdhury DR, Urban JF Jr., Zavala F, Kumar N. 2010. Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice. Vaccine 28:2917–23 [Google Scholar]
  119. Oertelt-Prigione S. 2012. The influence of sex and gender on the immune response. Autoimmun. Rev. 11:A479–85 [Google Scholar]
  120. Org E, Mehrabian M, Parks BW, Shipkova P, Liu X. et al. 2016. Sex differences and hormonal effects on gut microbiota composition in mice. Gut. Microbes 7:313–22 [Google Scholar]
  121. Pawelec G, Derhovanessian E. 2011. Role of CMV in immune senescence. Virus Res 157:175–79 [Google Scholar]
  122. Peto TJ, Mendy ME, Lowe Y, Webb EL, Whittle HC, Hall AJ. 2014. Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986–90) and in the nationwide immunisation program. BMC Infect. Dis. 14:7 [Google Scholar]
  123. Philipps J, Schonfeld C, Schleehauf DM, Beuerle W, Bienzle U, Kremsner PG. 1996. Side effects of travel vaccinations. Data collection via telephone survey in Berlin. Wien. Klin. Wochenschr. 108:615–20 [Google Scholar]
  124. Pietschmann P, Gollob E, Brosch S, Hahn P, Kudlacek S. et al. 2003. The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism. Exp. Gerontol. 38:1119–27 [Google Scholar]
  125. Pinheiro I, Dejager L, Libert C. 2011. X-chromosome-located microRNAs in immunity: Might they explain male/female differences? The X chromosome–genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females. BioEssays 33:791–802 [Google Scholar]
  126. Poland GA, Ovsyannikova IG, Kennedy RB, Lambert ND, Kirkland JL. 2014. A systems biology approach to the effect of aging, immunosenescence and vaccine response. Curr. Opin. Immunol. 29:62–68 [Google Scholar]
  127. Praharaj I, John SM, Bandyopadhyay R, Kang G. 2015. Probiotics, antibiotics and the immune responses to vaccines. Philos. Trans. R. Soc. B Biol. Sci. 370:20140144 [Google Scholar]
  128. Pulcini C, Massin S, Launay O, Verger P. 2013. Factors associated with vaccination for hepatitis B, pertussis, seasonal and pandemic influenza among French general practitioners: a 2010 survey. Vaccine 31:3943–49 [Google Scholar]
  129. Riner DK, Ndombi EM, Carter JM, Omondi A, Kittur N. et al. 2016. Schistosoma mansoni infection can jeopardize the duration of protective levels of antibody responses to immunizations against hepatitis B and tetanus toxoid. PLOS Negl. Trop. Dis. 10:e0005180 [Google Scholar]
  130. Rosic I, Malicevic S, Medic S. 2008. The significance of age and sex for the absence of immune response to hepatitis B vaccination. Srp. Arh. Celok. Lek. 136:33–37 [Google Scholar]
  131. Sankaran-Walters S, Macal M, Grishina I, Nagy L, Goulart L. et al. 2013. Sex differences matter in the gut: effect on mucosal immune activation and inflammation. Biol. Sex Differ. 4:10 [Google Scholar]
  132. Sartono E, Lisse IM, Terveer EM, van de Sande PJ, Whittle H. et al. 2010. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment. PLOS ONE 5:e10328 [Google Scholar]
  133. Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S. et al. 2009. Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J. Immunol. 182:5488–97 [Google Scholar]
  134. Seligman SJ. 2011. Yellow fever virus vaccine–associated deaths in young women. Emerg. Infect. Dis. 17:1891–93 [Google Scholar]
  135. Shann F. 2010. The non-specific effects of vaccines. Arch. Dis. Child 95:662–67 [Google Scholar]
  136. Sharma S, Eghbali M. 2014. Influence of sex differences on microRNA gene regulation in disease. Biol. Sex Differ. 5:3 [Google Scholar]
  137. Sinha A, Madden J, Ross-Degnan D, Soumerai S, Platt R. 2003. Reduced risk of neonatal respiratory infections among breastfed girls but not boys. Pediatrics 112:e303 [Google Scholar]
  138. Smithers-Sheedy H, Raynes-Greenow C, Badawi N, McIntyre S, Jones CA. et al. 2014. Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population-based study. Dev. Med. Child Neurol 56:846–52 [Google Scholar]
  139. Soneji S, Metlay J. 2011. Mortality reductions for older adults differ by race/ethnicity and gender since the introduction of adult and pediatric pneumococcal vaccines. Public Health Rep 126:259 [Google Scholar]
  140. Stanberry LR, Spruance SL, Cunningham AL, Bernstein DI, Mindel A. et al. 2002. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N. Engl. J. Med. 347:1652–61 [Google Scholar]
  141. Steegenga WT, Mischke M, Lute C, Boekschoten MV, Pruis MG. et al. 2014. Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice. Biol. Sex Differ. 5:11 [Google Scholar]
  142. Talaat KR, Greenberg ME, Lai MH, Hartel GF, Wichems CH. et al. 2010. A single dose of unadjuvanted novel 2009 H1N1 vaccine is immunogenic and well tolerated in young and elderly adults. J. Infect. Dis. 202:1327–37 [Google Scholar]
  143. Teixeira D, Longo-Maugeri IM, Santos JL, Duarte YA, Lebrao ML, Bueno V. 2011. Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from São Paulo city. Rev. Bras. Hematol. Hemoter. 33:367–71 [Google Scholar]
  144. Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H. et al. 2009. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum. Mol. Genet. 18:4046–53 [Google Scholar]
  145. Traub S, Demaria O, Chasson L, Serra F, Desnues B, Alexopoulou L. 2012. Sex bias in susceptibility to MCMV infection: implication of TLR9. PLOS ONE 7:e45171 [Google Scholar]
  146. Troy JD, Hill HR, Ewell MG, Frey SE. 2015. Sex difference in immune response to vaccination: a participant-level meta-analysis of randomized trials of IMVAMUNE smallpox vaccine. Vaccine 33:5425–31 [Google Scholar]
  147. Umlauf BJ, Haralambieva IH, Ovsyannikova IG, Kennedy RB, Pankratz VS. et al. 2012. Associations between demographic variables and multiple measles-specific innate and cell-mediated immune responses after measles vaccination. Viral. Immunol. 25:29–36 [Google Scholar]
  148. Urban BC, Roberts DJ. 2003. Inhibition of T cell function during malaria: implications for immunology and vaccinology. J. Exp. Med. 197:137–41 [Google Scholar]
  149. van der Heiden M, van Zelm MC, Bartol SJ, de Rond LG, Berbers GA. et al. 2016. Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females. Sci. Rep. 6:26892 [Google Scholar]
  150. Van Loveren H, Van Amsterdam JG, Vandebriel RJ, Kimman TG, Rumke HC. et al. 2001. Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environ. Health Perspect. 109:757–64 [Google Scholar]
  151. van Lunzen J, Altfeld M. 2014. Sex differences in infectious diseases—common but neglected. J. Infect. Dis. 209:Suppl. 379–80 [Google Scholar]
  152. Veenstra van Nieuwenhoven AL, Bouman A, Moes H, Heineman MJ, de Leij LF. et al. 2002. Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle. Fertil. Steril. 77:1032–37 [Google Scholar]
  153. Vermeiren AP, Hoebe CJ, Dukers-Muijrers NH. 2013. High non-responsiveness of males and the elderly to standard hepatitis B vaccination among a large cohort of healthy employees. J. Clin. Virol. 58:262–64 [Google Scholar]
  154. Vila-Córcoles A, Rodriguez T, de Diego C, Ochoa O, Valdivieso A. et al. 2007. Effect of influenza vaccine status on winter mortality in Spanish community-dwelling elderly people during 2002–2005 influenza periods. Vaccine 25:6699–707 [Google Scholar]
  155. Wang CS, Wang ST, Chou P. 2002. Efficacy and cost-effectiveness of influenza vaccination of the elderly in a densely populated and unvaccinated community. Vaccine 20:2494–99 [Google Scholar]
  156. Wang JJ, Wang J, Pang XY, Zhao LP, Tian L, Wang XP. 2016. Sex differences in colonization of gut microbiota from a man with short-term vegetarian and inulin-supplemented diet in germ-free mice. Sci. Rep. 6:36137 [Google Scholar]
  157. Watt AP, Loughlin L, Coyle PV. 2016. Congenital CMV disease—a female bias in Northern Ireland. J. Clin. Virol. 77:99–100 [Google Scholar]
  158. Weber SK, Schlagenhauf P. 2014. Childhood vaccination associated adverse events by sex: a literature review. Travel Med. Infect. Dis 12:459–80 [Google Scholar]
  159. Wegmann TG, Lin H, Guilbert L, Mosmann TR. 1993. Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon?. Immunol. Today 14:353–56 [Google Scholar]
  160. Wiemken TL, Carrico RM, Klein SL, Jonsson CB, Peyrani P. et al. 2014. The effectiveness of the polysaccharide pneumococcal vaccine for the prevention of hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia in the elderly differs between the sexes: results from the Community-Acquired Pneumonia Organization (CAPO) international cohort study. Vaccine 32:2198–203 [Google Scholar]
  161. Wikby A, Mansson IA, Johansson B, Strindhall J, Nilsson SE. 2008. The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age. Biogerontology 9:299–308 [Google Scholar]
  162. Wilson EB, Brooks DG. 2011. The role of IL-10 in regulating immunity to persistent viral infections. Curr. Top. Microbiol. Immunol. 350:39–65 [Google Scholar]
  163. Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P. et al. 2013. Gender bias in autoimmunity is influenced by microbiota. Immunity 39:400–12 [Google Scholar]
  164. Zeeshan M, Jabeen K, Ali AN, Ali AW, Farooqui SZ. et al. 2007. Evaluation of immune response to Hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study. BMC Infect. Dis. 7:120 [Google Scholar]
  165. Zhang X, Castelli FA, Zhu X, Wu M, Maillere B, BenMohamed L. 2008. Gender-dependent HLA-DR-restricted epitopes identified from herpes simplex virus type 1 glycoprotein D. Clin. Vaccine Immunol. 15:1436–49 [Google Scholar]
  166. Zhang Z, Chen L, Saito S, Kanagawa O, Sendo F. 2000. Possible modulation by male sex hormone of Th1/Th2 function in protection against Plasmodium chabaudi chabaudi AS infection in mice. Exp. Parasitol. 96:121–29 [Google Scholar]
  167. Zuckerman JN. 2006. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J. Med. Virol 78:169–77 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error