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

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.

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

10.26686/wgtn.14347367 ◽

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.

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Experimental human pneumococcal colonisation in older adults is feasible and safe, not immunogenic

10.1101/2020.04.23.20077073 ◽

2020 ◽

Author(s):

Hugh Adler ◽

Esther L German ◽

Elena Mitsi ◽

Elissavet Nikolaou ◽

Sherin Pojar ◽

...

Keyword(s):

Older Adults ◽

Immune Response ◽

Immune Responses ◽

Pneumococcal Disease ◽

Bacterial Culture ◽

Invasive Disease ◽

Post Challenge ◽

Nasal Wash ◽

Younger Adults ◽

Antibody Levels

Rationale: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonisation in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Measurements and Main Results: Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged 70 years and older. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7ug/mL (1.9-3.8) pre-challenge versus 3.0 (1.9-4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8ug/mL (2.0-3.9) to 2.2ug/mL (1.6-3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7-10.1) led to recolonisation in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.

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

Innovation in Aging ◽

10.1093/geroni/igaa057.869 ◽

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.

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

10.1101/2021.09.06.21263149 ◽

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.

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Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering

Scientific Reports ◽

10.1038/s41598-017-17735-x ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 14

Author(s):

Emily A. Voigt ◽

Diane E. Grill ◽

Michael T. Zimmermann ◽

Whitney L. Simon ◽

Inna G. Ovsyannikova ◽

...

Keyword(s):

Older Adults ◽

Immune Responses ◽

Influenza Vaccination ◽

Seasonal Influenza ◽

Data Driven ◽

Seasonal Influenza Vaccination ◽

Humoral Immune ◽

Humoral Immune Responses

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Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults Previously Vaccinated with a Live-Attenuated Herpes Zoster Vaccine: A Phase III, Group-Matched, Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1038 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S414-S414 ◽

Cited By ~ 3

Author(s):

Katrijn Grupping ◽

Laura Campora ◽

Martine Douha ◽

Thomas C Heineman ◽

Nicola P Klein ◽

...

Keyword(s):

Herpes Zoster ◽

Immune Responses ◽

Geometric Mean ◽

Primary Objective ◽

Phase Iii ◽

Zoster Vaccine ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Risk Increase ◽

Grant Recipient

Abstract Background Herpes zoster (HZ), caused by reactivation of varicella-zoster virus (VZV), typically manifests as a dermatomal rash and can lead to postherpetic neuralgia (PHN). HZ and PHN risk increase with age. Efficacy against HZ induced by a live-attenuated zoster vaccine (ZVL; Merck) declines following vaccination (21% in years 5–12 post-vaccination). To ensure protection, revaccination can be considered. Therefore, we assessed immunogenicity and safety of HZ/su, a non-live candidate vaccine containing VZV glycoprotein E (gE) subunit and AS01B adjuvant system (GSK), in adults previously vaccinated with ZVL ≥5 years before, (HZ-PreVac) compared with adults not vaccinated with ZVL (HZ-NonVac). Methods In this phase III, group-matched, open, multicenter study (NCT02581410), 2 parallel groups of adults ≥65 years of age (YOA) received 2 HZ/su doses 2 months apart. A co-primary objective was to compare humoral immune responses 1 month post-dose 2 (M3) in the 2 groups (non-inferiority criterion: upper limit [UL] of the 95% confidence interval [CI] for HZ-NonVac/HZ-PreVac adjusted anti-gE antibody geometric mean concentration [GMC] ratio <1.5). Humoral and cellular immune responses were evaluated at various time points. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post each dose, respectively. Serious AEs (SAEs), HZ cases and potential immune-mediated diseases (pIMDs) will be recorded until study end. Here, we present data up to M3, as the study is still ongoing. Results 430 participants were vaccinated. M3 humoral immune responses in HZ-PreVac were non-inferior to those in HZ-NonVac and the co-primary objective was met as the UL of the 95% CI of the adjusted GMC ratio was 1.17 (Table 1). In addition, there were no apparent differences in CD4[2+] T-cell frequencies between groups (Figure 1). No clinically meaningful differences between frequencies of solicited AEs, unsolicited AEs or SAEs in the 2 groups were observed (Table 2). No SAEs considered vaccine-related by investigators, no suspected HZ cases and no pIMDs were reported up to M3. Conclusion HZ/su vaccination in adults ≥65 YOA who previously received ZVL stimulates strong immune responses and does not raise safety concerns. Funding GlaxoSmithKline Biologicals SA Disclosures K. Grupping, GSK group of companies: Employee, Salary; L. Campora, GSK group of companies: Employee, Salary; M. Douha, GSK group of companies: Employee, Salary; T. C. Heineman, GSK group of companies: Consultant and Shareholder, Consulting fee; N. P. Klein, GSK group of companies: Investigator, Grant recipient sanofi pasteur: Investigator, Grant recipient; Merck & Co: Investigator, Grant recipient; MedImmune: Investigator, Grant recipient; Protein Science: Investigator, Grant recipient; Pfizer: Investigator, Grant recipient; H. Lal, Pfizer: Employee and Shareholder, Salary and Stock as part of compensation; GSK group of companies: Employee at the time of study and Shareholder, Salary and Stock as part of compensation; J. Peterson, GSK group of companies: Investigator, Principal investigator fees; L. Oostvogels, GSK group of companies: Employee and Shareholder, Salary and Shares

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Humoral Immune Responses in the Tropical-Splenomegaly Syndrome in New Guinea

Clinical Science ◽

10.1042/cs0430869 ◽

1972 ◽

Vol 43 (6) ◽

pp. 869-879 ◽

Cited By ~ 7

Author(s):

G. G. Crane ◽

Merrill J. Rowley ◽

M. F. Warburton ◽

I. R. Mackay

Keyword(s):

Immune Responses ◽

Influenza Vaccine ◽

Geometric Mean ◽

Secondary Response ◽

Primary Immune Response ◽

Post Inoculation ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Immune Capacity ◽

Increased Susceptibility

1. Humoral immune capacity was measured in New Guineans with tropical splenomegaly or who had been splenectomized for this disease, to assess relationships between tropical splenomegaly and immunological function; the test antigens were flagellin and monovalent influenza vaccine. 2. Controls included age- and sex-matched healthy and hospitalized Caucasians, and comparative data on responses to flagellin were available for New Guinean school children. 3. For flagellin, geometric mean titres in the primary immune response in New Guineans with tropical splenomegaly were significantly lower than those of other groups, whereas pre-immunization titres and those obtained during the secondary response were comparable. 4. For influenza vaccine, both pre-inoculation and peak mean post-inoculation titres of antibody were significantly lower in New Guineans, attributable possibly to lack of previous exposure to this antigen. 5. The low primary antibody responses in New Guineans with tropical splenomegaly could result from pre-emption of antibody-producing tissues arising from abnormal demands for antimalarial antibody; this may determine the increased susceptibility to, and high mortality from, bacterial infection in tropical splenomegaly.

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