Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults

Jackson, Simon A.; Lentino, Joseph R.; Kopp, James; Murray, Linda; Ellison, W.; Rhee, Margaret; Shockey, Gerald; Akella, Lalith; Erby, Kimberly; Heyward, William L.; Janssen, Robert S.

doi:10.1016/j.vaccine.2017.12.038

Cited by 153 publications

(127 citation statements)

References 29 publications

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“…Some of the challenges of vaccination in the elderly population may be overcome by more potent adjuvants, such as the CpG-adjuvanted Heplisav-B which achieved seroprotection rates > 90% [13]. However, the molecular mechanisms that underly immunesenescence are complex and understanding of these mechanisms continues to evolve.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, primary immunizations against HBV are recommended for high risk groups including patients requiring dialysis, receiving immunosuppression therapy, those affected with chronic liver disease, HIV, HCV, or travelers [10]. Reduced rates of protection (Ab responses ≥10 IU/ml) have been reported in volunteers > 60 years of age receiving alumadjuvanted HBV vaccines, ranging from 34% in the frail elderly to 72% in clinical trial populations [11][12][13]. Despite the lower protection rates following primary vaccination for HBV, booster responses for older adults (> 65 years) after re-vaccination (for individuals with documented vaccination > 10 years prior) appear to be intact in elderly, suggesting that the ability of T cells to generate lasting memory following a di novo vaccination declines with age [14].…”

Section: Introductionmentioning

confidence: 99%

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The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

et al. 2020

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Background: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cellmediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions.Results: Fifty-two healthy, community dwelling elderly adults (65-82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alumadjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21-34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. Conclusions: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B-and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

et al. 2020

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“…The increase in seroprotection rates was 25% (95% CI, 19%e31%). 52 HepB-CpG is administered in two doses, with the second dose 30 days after the first.…”

Section: Diabetesmentioning

confidence: 99%

Immunization Strategies to Span the Spectrum of Immunocompromised Adults

Whitaker

2020

Mayo Clinic Proceedings

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The Advisory Committee on Immunization Practices to the US Centers for Disease Control and Prevention provides annual recommendations for routine adult immunizations. Many recommendations consider patient factors such as age, medical conditions, and medications that increase an individual's risk for infection with a vaccine-preventable disease. These factors, particularly those that lead to immunocompromise, may also alter the risk-benefit ratio for live vaccines, and/or lead to decreased vaccine immunogenicity and effectiveness. The provider may need to consider alternative vaccination strategies, including higher antigen dose vaccines, adjuvanted vaccines, avoidance of live vaccines, and careful timing of vaccination to optimize safety and effectiveness in immunocompromised populations. This thematic review discusses general principles regarding immunization of adults across the spectrum of immunocompromise, examines current guidelines and studies that support them, and outlines future research needs.

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“…Synthetic CpG oligodeoxynucleotides (ODNs) are TLR-9 agonists able to induce type I IFNs as well as proinflammatory cytokine production, generating Th1 type cellular and humoral immune responses [12,13]. Recently, the CpG-ODN was approved for the first time for application in humans, and Heplisav-B, a hepatitis B vaccine containing CpG-ODN as an adjuvant, was approved by the United States Food and Drug Administration [14]. Imiquimod, is a synthetic TLR7/8 agonist, reported to induce an adjuvant activity able to boost antigen-specific humoral and Th1 type cellular immune responses [15,16].…”

Section: Introductionmentioning

confidence: 99%

Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy

et al. 2020

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Background:We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant ® , a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.Methods: PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant ® ) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4 + T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM.

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Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults

Cited by 153 publications

References 29 publications

The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

Immunization Strategies to Span the Spectrum of Immunocompromised Adults

Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy

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