An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

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2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

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Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

TLR-based immune adjuvants.

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease.

Chapter 2: Innate Immunity

The immunostimulants 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and the saponin QS-21 are part of licensed or candidate vaccines. MPL and QS-21 directly affect the innate immune response to orchestrate the quality and intensity of the adaptive immune response to the vaccine antigens. The combination of immunostimulants in different adjuvant formulations forms the basis of Adjuvant Systems (AS) as a way to promote appropriate protective immune responses following vaccination. MPL and aluminum salts are present in AS04, and both MPL and QS-21 are present in AS01 and AS02, which are liposome- and emulsion-based formulations, respectively. The recent clinical performance of AS01-, AS02- and AS04-adjuvanted vaccines will be discussed in the context of the diseases being targeted. The licensing of two AS04-adjuvanted vaccines and the initiation of Phase III trials with an AS01-adjuvanted vaccine demonstrate the potential to develop new or improved human vaccines that contain MPL or MPL and QS-21.

Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems

https://www.kidney-international.org/article/S0085-2538(15)53084-6/pdf

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients. Commentary

Background. Transmission of hepatitis B virus (HBV) from carrier mothers to their babies appears to be one of the most important factors influencing the prevalence of chronic HBV infection in areas of high hepatitis B endemicity. Methods. Infants born to HBV surface antigen (HBsAg)―positive mothers who were or were not positive for HBV e antigen (HBeAg) or to mothers who were negative for both HBsAg and HBeAg have been followed for 17 years for serological evidence of HBV infection. These infants were divided into 2 groups on the basis of their hepatitis B vaccination protocols: group 1 received vaccine at birth and 1, 2, and 12 months later, and group 2 received vaccine at birth and 1 and 6 months later. Follow-up involved annual clinic visits, during which a blood sample was taken and analyzed for the presence of HBsAg, antibody to HBsAg, and antibody to HBV core antigen (HBcAg). Selected blood samples that tested positive for HBV markers during ≥2 consecutive visits separated by a long interval were further investigated by polymerase chain reaction to detect HBV DNA. Results. Transient presence of HBsAg or transient and/or long-term presence of antibody to HBcAg suggested that this population was heavily exposed to HBV during the follow-up period. Despite these findings, no new cases of chronic HBV infection were observed. None of the subjects with transient presence of HBsAg had any clinical symptoms of liver disease. Conclusions. This study demonstrates the efficacy of the HBV vaccine and its ability to protect against symptomatic disease.

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Long‐Term Benefit of Hepatitis B Vaccination among Children in Thailand with Transient Hepatitis B Virus Infection Who Were Born to Hepatitis B Surface Antigen–Positive Mothers

Thiomersal has been used as preservative in multi-dose vials of hepatitis B vaccine (Engerix-B) Due to safety concerns, thiomersal was replaced with 2-phenoxyethanol (2PE) as preservative in multi-dose vials The potency of 2PE preserved hepatitis B vaccine multiple use vials was measured over the shelf-life in terms of immunogenicity, reactogenicity and safety This single-blind, randomized study was conducted with the assistance of employees of GlaxoSmithKline Biologicals, makers of the Engerix-B vaccine Four hundred twenty subjects aged > or =18 years were randomized to receive three doses (0, 1, 6 months) of 2PE preserved hepatitis B vaccine kept on the shelf 18 months (2PE Old group), or thiomersal preserved hepatitis B vaccine [HBV(Thio) group] Anti-HBs was measured by GlaxoSmithKline Biologicals post-vaccination; the reactogenicity and safety of the vaccines were assessed Protective anti-HBs levels (> or =10 mIU/ml) were measured one month after dose 3 The results showed protective levels in 868% (2PE New), 89% (2PE Old) and 953% [HBV(Thio)] There was no difference detected between the 2PE New and 2PE Old groups in terms of anti-HBs seroprotection rates and geometric mean concentrations one month after dose 3 However, both 2PE groups had significantly lower seroprotection rates than the HBV(Thio) group and the number of non-responders was higher in the 2PE groups than in the Thio group A antibody response rates over time were similar between the 2PE New and Old groups The reactogenicity profiles were acceptable and the ranges were similar for each group The shelf-life of the vaccines had no impact on immunogenicity or reactogenicity and 2PE preserved hepatitis B vaccine can be considered stable over time

Immunogenicity of HBV vaccine during stated shelf-life.

One hundred two patients aged 2-43 years diagnosed with acute malaria due to P. falciparum or P. vivax were treated with 3 doses of halofantrine (500 mg for ≥18 year old patients and 8 mg/kg of patient body weight for 2-17 year olds), with each dose administered once in 6 hours and followed up for 28 days. Out of 102 patients 63 had P. falciparum, 36 had P. vivax and 3 had unidentified species. Following three dose therapy, 96.1% (98/102) of pa- tients were cured, 0.98% (1/102) showed improvement from baseline, 1.96% (2/102) did not respond and were considered as treatment failures and one patient had indeterminate data. The lone patient, who relapsed after 120 hours post dose 1, was cured following re-treatment on day 7. The median parasite clearance and fever clearance times, from the first dose, were 26 hours and 30 hours, respectively. Eleven point eight percent (12/102) of patients reported adverse events, of which abdominal pain, reported by one subject, was considered to be probably related to the drug and required corrective therapy. There were no serious adverse events or fatalities and none of the patients had a change in QT c interval greater than 10%. Thirteen point seven percent (14/102) of patients had abnormal clinical laboratory parameters that normalized later.

Karthik Srinivasa

Papers

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients. Commentary

Long‐Term Benefit of Hepatitis B Vaccination among Children in Thailand with Transient Hepatitis B Virus Infection Who Were Born to Hepatitis B Surface Antigen–Positive Mothers

Immunogenicity of HBV vaccine during stated shelf-life.

Efficacy and safety of halofantrine in Pakistani children and adults with malaria caused by P. falciparum and P. vivax.