scholarly journals Reduced magnitude and durability of humoral immune responses by COVID-19 mRNA vaccines among older adults

2021 ◽  
Author(s):  
Mark A. Brockman ◽  
Francis M. Mwimanzi ◽  
Hope R. Lapointe ◽  
Yurou Sang ◽  
Olga Agafitei ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
The Elderly ◽  
Antibody Responses ◽  
Chronic Health ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titers ◽  
Binding Antibody ◽  
Dose Responses

Background mRNA vaccines reduce COVID-19 incidence and severity, but the durability of vaccine-induced immune responses, particularly among the elderly, remains incompletely characterized. Methods Anti-spike RBD antibody titers, ACE2 competition and virus neutralizing activities were longitudinally assessed in 151 healthcare workers and older adults (overall aged 24-98 years) up to three months after vaccination. Results Older adults exhibited lower antibody responses after one and two vaccine doses for all measures. In multivariable analyses correcting for sociodemographic, chronic health and vaccine-related variables, age remained independently associated with all response outcomes. The number of chronic health conditions was additionally associated with lower binding antibody responses after two doses, and male sex with lower ACE2 competition activity after one dose. Responses waned universally at three months after the second dose, but binding antibodies, ACE2 competition and neutralizing activities remained significantly lower with age. Older adults also displayed reduced ability to block ACE2 binding by the Delta variant. Conclusions The humoral immune response to COVID-19 mRNA vaccines is significantly weaker with age, and universally wanes over time. This will likely reduce antibody-mediated protection against SARS-CoV-2 and the Delta variant as the pandemic progresses. Older adults may benefit from additional immunizations as a priority.

scholarly journals Intersection of Sex and Frailty in Humoral Immune Responses to Influenza Vaccine in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 271-272
Author(s):  
Janna Shapiro ◽  
Helen Kuo ◽  
Rosemary Morgan ◽  
Huifen Li ◽  
Sabra Klein ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza A ◽  
Community Dwelling ◽  
Influenza Vaccines ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
High Dose ◽  
Humoral Immune ◽  
Humoral Immune Responses

Abstract Older adults bear the highest burden of severe disease and complications associated with seasonal influenza, with annual vaccination serving as the best option for protection. Variability in vaccine efficacy exists, yet the host factors that affect immune responses to inactivated influenza vaccines (IIV) are incompletely understood. We hypothesized that sex and frailty interact to affect vaccine-induced humoral responses among older adults. To test this hypothesis, community-dwelling adults above 75 years of age were recruited yearly, assessed for frailty (as defined by the Cardiovascular Health Study criteria), and vaccinated with the high-dose trivalent IIV. Humoral immune responses were evaluated via hemagglutination inhibition titers. The study began during the 2014-2015 influenza season, with yearly cohorts ranging from 76-163 individuals. A total of 617 vaccinations were delivered from 2014-2019. In preliminary analyses, the outcome of interest was seroconversion, defined as ≥ 4-fold rise in titers. Crude odds ratios suggest that females are more likely to seroconvert to influenza A strains (H1N1: OR = 1.39, (0.98-1.96) ; H3N2: 1.17 (0.85 – 1.62)), while males are more likely to seroconvert to the B strain (OR = 0.85 (0.60 – 1.22)). Furthermore, this sex difference was modified by frailty – for example, the odds of seroconversion to H1N1 were 65% higher for females than males among those who were nonfrail, and only 30% higher among females who were frail. Together, these results suggest that sex and frailty interact to impact immune responses to influenza vaccines. These findings may be leveraged to better protect vulnerable populations.

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 Immunological Distinctions between Acellular and Whole-Cell Pertussis Immunizations of Baboons Persist for at Least One Year after Acellular Vaccine Boosting

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 729
Author(s):  
Leah E. Cole ◽  
Jinrong Zhang ◽  
Kristl M. Pacheco ◽  
Philippe Lhéritier ◽  
Natalie G. Anosova ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Burden ◽  
Memory B Cells ◽  
Whole Cell ◽  
Humoral Immune ◽  
Serum Bactericidal Activity ◽  
Humoral Immune Responses ◽  
Specific Memory ◽  
Antibody Titers ◽  
One Year

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting.

scholarly journals Experimental human pneumococcal colonization in older adults is feasible and safe, not immunogenic

2021 ◽  
Author(s):  
H Adler ◽  
EL German ◽  
E Mitsi ◽  
E Nikolaou ◽  
S Pojar ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Pneumococcal Disease ◽  
Geometric Mean ◽  
Invasive Disease ◽  
Younger Adults ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Pneumococcal Colonization ◽  
Successful Colonization

Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations. Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged >70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotypespecific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 mg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 mg/ml (2.0-3.9) to 2.2 mg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.

scholarly journals Experimental human pneumococcal colonization in older adults is feasible and safe, not immunogenic

2021 ◽  
Author(s):  
H Adler ◽  
EL German ◽  
E Mitsi ◽  
E Nikolaou ◽  
S Pojar ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Pneumococcal Disease ◽  
Geometric Mean ◽  
Invasive Disease ◽  
Younger Adults ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Pneumococcal Colonization ◽  
Successful Colonization

Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations. Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged >70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotypespecific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 mg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 mg/ml (2.0-3.9) to 2.2 mg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.

scholarly journals Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeae during Uncomplicated Genital Infections

1999 ◽  
Vol 67 (8) ◽  
pp. 3937-3946 ◽  
Author(s):  
Spencer R. Hedges ◽  
Matthew S. Mayo ◽  
Jiri Mestecky ◽  
Edward W. Hook ◽  
Michael W. Russell
Keyword(s):  
Immune Responses ◽  
Transmitted Disease ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genital Infections ◽  
Sexually Transmitted ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Repeated Infections ◽  
Antibody Levels

ABSTRACT Repeated infections with Neisseria gonorrhoeae are common among patients attending sexually transmitted disease clinics. We examined whether previous infections or site of infection altered the local and systemic antigonococcal antibody levels in males and females. Antibodies against N. gonorrhoeae MS11 and the patients’ homologous infecting isolates were measured by enzyme-linked immunosorbent assay. In general, the local and systemic immune responses to gonococci were extremely modest. There was a slight increase in serum immunoglobulin G (IgG) against the MS11 strain and the homologous isolates in infected males. Levels of serum IgA1 antibodies against MS11 were slightly higher in infected than in uninfected females. A history of previous infections with N. gonorrhoeae did not alter the antibody levels in patients with a current infection, suggesting that immunological memory is not induced by uncomplicated gonococcal infections. Antibody responses to infected subjects’ homologous isolates were observed in cervical mucus; IgA1 levels increased while IgG levels decreased. The decline in mucosal IgG against the homologous isolates was less common in subjects having both rectal and cervical infections; otherwise, no effect of rectal involvement was observed. The absence of substantially higher antibody levels to gonococci where there is infection at a site known to contain organized lymphoid tissue suggests that the low levels of responses to uncomplicated infections may not be due simply to an absence of inductive sites in the genital tract. We propose that in addition to its potential ability to avoid the effects of an immune response,N. gonorrhoeae does not elicit strong humoral immune responses during uncomplicated genital infections.

scholarly journals Effect of mannanoligosaccharides and/or enzymes on antibody titers against infectious bursal and Newcastle disease viruses

2009 ◽  
Vol 61 (1) ◽  
pp. 6-11 ◽  
Author(s):  
M.C. Oliveira ◽  
D.F. Figueiredo-Lima ◽  
D.E. Faria Filho ◽  
R.H. Marques ◽  
V.M.B. Moraes
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Control Diet ◽  
Positive Control ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Randomized Experimental Design ◽  
Bursal Disease ◽  
Antibody Titers

The effect of including mannanoligosaccharides (MOS) and/or enzymes in broiler diets on antibody titers against infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) was evaluated. A total of 750 broilers were distributed into a completely randomized experimental design in a factorial arrangement 2 x 2 + 1 with two levels of MOS (0 and 0.1% until 21 days and 0.05% from 22 to 42 days of age), two levels of enzymes (0 and 0.05%) and a positive control diet containing antibiotic, totaling five treatments with five replicates each. For antibody analyses, blood samples were weekly collected by jugular vein puncture in the same two birds per replicate. The first and last collections were done at 7 and 42 days of age, respectively. The inclusion of MOS resulted in increased antibody titers against IBDV in the fourth (P<0.03) and fifth (P<0.02) weeks, and against NDV in the third (P<0.01), fourth (P<0.03) and fifth (P<0.03) weeks of age. MOS was effective in stimulating the humoral immune responses against IBDV and NDV vaccine viruses.

Regulation of humoral immunity in rats by pituitary hormones

1981 ◽  
Vol 98 (4) ◽  
pp. 506-513 ◽  
Author(s):  
Istvan Berczi ◽  
Eva Nagy ◽  
Kalman Kovacs ◽  
Eva Horvath
Keyword(s):  
Immune Responses ◽  
Antibody Formation ◽  
Pituitary Hormones ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
E Coli ◽  
Humoral Immune ◽  
Fischer 344 ◽  
Humoral Immune Responses ◽  
Hypophysectomized Rats

Abstract. Hypophysectomized female Fischer 344 and Wistar-Furth rats had severely impaired primary and secondary antibody responses to sheep red blood cells (SRBC). Mercaptoethanol-sensitive (IgM) and mercaptoethanol-resistant (IgG) antibodies were similarly affected. Titers to E. Coli 055:B5 lipopolysaccharide were also significantly decreased in such animals. The antibody response of hypophysectomized rats could be restored by syngeneic pituitary grafts when placed under the kidney capsule or by prolactin treatment. Growth hormone was less effective in this respect than prolactin. Treatment of normal rats with ACTH suppressed their antibody formation to SRBC. These results indicate that the pituitary gland has the potential to regulate humoral immune responses.

scholarly journals Humoral immune responses to periodontal pathogens in the elderly

2015 ◽  
Vol 45 (5) ◽  
pp. 178 ◽  
Author(s):  
Uttom Shet ◽  
Hee-Kyun Oh ◽  
Hyun-Ju Chung ◽  
Young-Joon Kim ◽  
Ok-Su Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Periodontal Pathogens ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Cellular and Humoral Immune Responses toBorrelia burgdorferi Antigens in Patients with Culture-Positive Early Lyme Disease

2001 ◽  
Vol 69 (12) ◽  
pp. 7437-7444 ◽  
Author(s):  
Austin Vaz ◽  
Lisa Glickstein ◽  
Jodie A. Field ◽  
Gail McHugh ◽  
Vijay K. Sikand ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Immune Responses ◽  
Erythema Migrans ◽  
Antibody Responses ◽  
Humoral Immune ◽  
Convalescent Phase ◽  
Humoral Immune Responses ◽  
Antibody Reactivity ◽  
Disseminated Disease ◽  
Culture Positive

ABSTRACT We determined cellular and humoral immune responses toBorrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

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