Sex differences in vaccine-induced humoral immunity

Fischinger, Stephanie; Boudreau, Carolyn M.; Butler, Audrey L.; Streeck, Hendrik; Alter, Galit

doi:10.1007/s00281-018-0726-5

Cited by 333 publications

(308 citation statements)

References 103 publications

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“…Hence, we could not exclude that vaccination coverage against MMR on St. Eustatius was slightly higher in women as compared to men. Conversely, given the higher GMC in women too, women might serologically respond better to the vaccine components, as postulated by others [26,27]. Nonetheless, as cellular immunity is assumed to be an essential part of protection [28], higher risk of susceptibility among vaccinated men remains questionable.…”

Section: Discussionmentioning

confidence: 95%

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands

et al. 2019

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The National Immunization Program (NIP) on Bonaire, St. Eustatius and Saba (i.e., Caribbean Netherlands (CN)) includes the measles‐mumps‐rubella (MMR) vaccine since 1988/89. Seroepidemiological data is an important tool to evaluate the NIP, hence a cross-sectional representative population-based serosurveillance study was conducted for the first time in CN in mid-2017. Participants (n = 1829, aged 0–90 years) donated a blood sample and completed a health-related questionnaire. MMR-specific IgG antibodies were determined using a bead-based multiplex immunoassay and risk factors were analyzed using logistic regression models. Overall seroprevalence was high for measles (94%), but lower for mumps and rubella (both 85%). In NIP eligibles, including women of childbearing age, rubella seroprevalence (88%) exceeded the threshold for protection (85%); however, for measles (89%) this protective level (95%) was not met. MMR seropositivity was lowest in children who became CN resident at 11–17 years of age (especially for measles (72%)), mostly originating from Latin America and other non-Western countries. Interestingly, rubella seroprevalence was lowest in non-NIP eligible adults from Dutch overseas territories and Suriname (75%). Taken together, MMR immunity is generally good in CN, nonetheless some risk groups were identified. Additionally, we found evidence for a unique island epidemiology. In light of recent regional measles outbreaks, disease monitoring remains of utmost importance.

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Section: Discussionmentioning

confidence: 95%

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands

et al. 2019

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“…Males and females display differential immunological responses to foreign-and self-antigens (7,12,60). Antibody responses to infections as well as bacterial and viral vaccines, such as influenza, hepatitis A, hepatitis B, rubella, measles, diphtheria, tetanus, Brucella, and rabies vaccines, are generally more vigorous in females than males (5,(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75). Consistent with these differences, females show lower incidence of clinical disease than males after vaccination with influenza (76-79), hepatitis A (80,81), and hepatitis B (82) vaccines.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a

Casali

Shen

et al. 2020

Front. Immunol.

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Estrogen contributes to females' strong antibody response to microbial vaccines and proneness to autoimmunity, particularly antibody-mediated systemic autoimmunity, in females. We have hypothesized that this is due to estrogen-mediated potentiation of class switch DNA recombination (CSR) and somatic hypermutation (SHM). As we have shown, estrogen boosts AID expression, which is critical for both CSR and SHM, through upregulation of HoxC4, which together with NF-κB critically mediates Aicda (AID gene) promoter activation. We contend here that additional regulation of Aicda expression by estrogen occurs through epigenetic mechanisms. As we have shown, histone deacetylase inhibitors (HDIs) short-chain fatty acid (SCFA) butyrate and propionate as well as the pharmacologic HDI valproic acid upregulate miRNAs that silence AID expression, thereby modulating specific antibody responses in C57BL/6 mice and autoantibody responses in lupus-prone MRL/Fas lpr/lpr mice. Here, using constitutive knockout Esr1 −/− mice and B cells as well as conditional knockout Aicda cre/cre Esr1 flox/flox mice and B cells, we showed that the HDI-mediated downregulation of Aicda expression as well as the maturation of antibody and autoantibody responses is reversed by estrogen and enhanced by deletion of ERα or E2 inhibition. Estrogen's reversion of HDI-mediated inhibition of Aicda and CSR in antibody and autoantibody responses occurred through downregulation of B cell miR-26a, which, as we showed, targets Aicda mRNA 3 ′ UTR. miR-26a was significantly upregulated by HDIs. Accordingly, enforced expression of miR-26a reduced Aicda expression and CSR, while miR-26a-sponges (competitive inhibitors of miR-26a) increased Aicda expression and CSR. Thus, our findings show that estrogen reverses the HDI-mediated downregulation of AID expression and CSR through selective modulation of miR-26a. They also provide mechanistic insights into the immunomodulatory activity of this hormone and a proof-of-principle for using combined ER inhibitor-HDI as a potential therapeutic approach.

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“…132,147 Studies show that females exhibit stronger immune responses to immunization compared to males. 148,149 There are differential antibody responses to rubella and measles viral protein between males and females and that both hormonal and genetic difference may be influencing the immune responses. 148,150,151 Practical issues may stand in the way of achieving this new development (personalized vaccinology).…”

Section: The Subpopulation Levelmentioning

confidence: 99%

“…148,149 There are differential antibody responses to rubella and measles viral protein between males and females and that both hormonal and genetic difference may be influencing the immune responses. 148,150,151 Practical issues may stand in the way of achieving this new development (personalized vaccinology). Having to use different vaccines for different persons based because of personal genetic composition requires more time and labor during the vaccination process.…”

Section: The Subpopulation Levelmentioning

confidence: 99%

<p>Immunoinformatics and Vaccine Development: An Overview</p>

Oli

Obialor

Ifeanyichukwu

et al. 2020

ITT

177

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The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/reemerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

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Sex differences in vaccine-induced humoral immunity

Cited by 333 publications

References 103 publications

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands

Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a

<p>Immunoinformatics and Vaccine Development: An Overview</p>

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