scholarly journals Genetic factors and age are the strongest predictors of humoral immune responses to common pathogens and vaccines

2018 ◽  
Author(s):  
Petar Scepanovic ◽  
Cécile Alanio ◽  
Christian Hammer ◽  
Flavia Hodel ◽  
Jacob Bergstedt ◽  
...  
Keyword(s):  
Immune Responses ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Humoral Response ◽  
Genome Wide Association ◽  
Healthy Individuals ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Genome Wide ◽  
Age And Sex

AbstractIntroductionHumoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that human genetic variation influences (i) serum immunoglobulin levels, (ii) seroconversion rates, and (iii) intensity of antigen-specific immune responses. Here, we evaluate the impact of intrinsic (age and sex), environmental and genetic factors on the variability of humoral response to common pathogens and vaccines.MethodsWe characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age‐ and sex-stratified cohort of 1,000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 & 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~5 million genetic variants and antibody responses using single marker and gene burden tests.Results and discussionWe identified age and sex as important determinants of humoral response, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leucocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations.ConclusionsUsing extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrate that age, sex and specific human genetic variants contribute to inter-individual variability in humoral response. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

2021 ◽  
Author(s):  
Paulina Kaplonek ◽  
Deniz Cizmeci ◽  
Stephanie Fischinger ◽  
Ai-ris Collier ◽  
Todd Suscovich ◽  
...  
Keyword(s):  
Immune Responses ◽  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Hospital Staff ◽  
Differential Protection ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Functional Antibodies ◽  
Functional Profiles

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the post-boost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitope-specific responses, with higher RBD- and NTD- specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

scholarly journals A Genome-Wide Association Study of Novel Genetic Variants Associated With Anthropometric Traits in Koreans

2021 ◽  
Vol 12 ◽  
Author(s):  
Hye-Won Cho ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Genetic Variants ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Fat Distribution ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

scholarly journals Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization

2000 ◽  
Vol 74 (6) ◽  
pp. 2620-2627 ◽  
Author(s):  
Daniel E. Hassett ◽  
Jie Zhang ◽  
Mark Slifka ◽  
J. Lindsay Whitton
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Ex Vivo ◽  
Humoral Response ◽  
Dna Vaccination ◽  
Protective Capacity ◽  
Live Virus ◽  
Virus Challenge ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACT Virus infections are devastating to neonates, and the induction of active antiviral immunity in this age group is an important goal. Here, we show that a single neonatal DNA vaccination induces cellular and humoral immune responses which are maintained for a significant part of the animal's life span. We employ a sensitive technique which permits the first demonstration and quantitation, directly ex vivo, of virus-specific CD8+ T cells induced by DNA immunization. One year postvaccination, antigen-specific CD8+ T cells were readily detectable and constituted 0.5 to 1% of all CD8+ T cells. By several criteria—including cytokine production, perforin content, development of lytic ability, and protective capacity—DNA vaccine-induced CD8+ memory T cells were indistinguishable from memory cells induced by immunization with a conventional (live-virus) vaccine. Analyses of long-term humoral immune responses revealed that, in contrast to the strong immunoglobulin G2a (IgG2a) skewing of the humoral response seen after conventional vaccination, IgG1 and IgG2a levels were similar in DNA-vaccinated neonatal and adult animals, indicating a balanced T helper response. Collectively, these results show that a single DNA vaccination within hours or days of birth can induce long-lasting CD8+ T- and B-cell responses; there is no need for secondary immunization (boosting). Furthermore, the observed immune responses induced in neonates and in adults are indistinguishable by several criteria, including protection against virus challenge.

scholarly journals Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Petar Scepanovic ◽  
◽  
Cécile Alanio ◽  
Christian Hammer ◽  
Flavia Hodel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Genetic Variants ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Identifying the MAGUK Protein Carma-1 as a Central Regulator of Humoral Immune Responses and Atopy by Genome-Wide Mouse Mutagenesis

Immunity ◽  
2003 ◽  
Vol 18 (6) ◽  
pp. 751-762 ◽  
Author(s):  
Jesse E. Jun ◽  
Lauren E. Wilson ◽  
Carola G. Vinuesa ◽  
Sylvie Lesage ◽  
Mathieu Blery ◽  
...  
Keyword(s):  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Genome Wide ◽  
Maguk Protein ◽  
Mouse Mutagenesis

Variation in class-specific humoral immune responses of different mouse strains to microfilariae ofDipetalonema viteae

Parasitology ◽  
1987 ◽  
Vol 95 (3) ◽  
pp. 559-568 ◽  
Author(s):  
N. M. Almond ◽  
M. J. Worms ◽  
W. Harnett ◽  
R. M. E. Parkhouse
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Significant Variation ◽  
Humoral Response ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Subcutaneous Transplantation ◽  
Dipetalonema Viteae

SUMMARYThe class-specific antibody responses of 3 strains of mice (C57/Bl10, BALB/C and CBA/N) known to vary in their ability to control the microfilaraemia which follows the subcutaneous transplantation of adult femaleDipetalonema viteaehas been investigated. The 3 mouse strains showed significant variation (a) in total levels of immunoglobulins and (b) in ability to recognize individual radio-isotope-labelled antigens as measured by coprecipitation. Within each mouse strain it was noted that antigens could vary with respect to the nature of the isotype of the antibody response which they elicited. Furthermore, by comparing results obtained from class-specific coprecipitation with surface ELISA it was found that a similar variation between responses to individual epitopes was also likely. No differences were observed in the humoral response of the 3 mouse strains which could explain the known resistance of the C57/B110 strain; reasons for this are discussed.

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