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Use of licensed vaccines for active immunization of the immunocompromised host.

ABSTRACT: The latter part of the 20th century has witnessed an unprecedented rise in the number of individuals with impaired immunity. This is primarily attributable to the increased development and use of antineoplastic therapy for malignancies, organ and bone marrow transplantation, and the AIDS epidemic. Individuals with impaired immunity are often at increased risk for infections, and they can experience more severe and complicated courses of infection. The lack of therapy for a variety of viruses and the rise in antimicrobial resistance of many pathogens have focused attention on vaccination to prevent infectious diseases. The efficacy of most licensed vaccines has been established in immunocompetent hosts. However, there is also considerable experience with most vaccines in those with impaired immunity. We reviewed the use of licensed live, inactivated, and polysaccharide vaccines in this group, and several themes emerged: (i) most vaccines are less immunogenic in those with impaired immunity than in normal individuals; (ii) live vaccines are generally contraindicated in this group; and (iii) the efficacy of many commonly used vaccines has not been established in people with impaired immunity. This review suggests that for most vaccines there are little or no efficacy data in those with impaired immunity but their use in this patient group is generally safe.

SUBMITTER: Pirofski LA

PROVIDER: S-EPMC121373 | biostudies-other | 1998 Jan

REPOSITORIES: biostudies-other

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Use of licensed vaccines for active immunization of the immunocompromised host.

Pirofski L A LA Casadevall A A

Clinical microbiology reviews 19980101 1

The latter part of the 20th century has witnessed an unprecedented rise in the number of individuals with impaired immunity. This is primarily attributable to the increased development and use of antineoplastic therapy for malignancies, organ and bone marrow transplantation, and the AIDS epidemic. Individuals with impaired immunity are often at increased risk for infections, and they can experience more severe and complicated courses of infection. The lack of therapy for a variety of viruses and ...[more]

PMID: 9457426

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Project description:Human papillomavirus (HPV) infections are the most common sexually transmitted infections. In the absence of vaccination, it is estimated that 75% of sexually active Canadians will have an HPV infection at some point in their lives. HPV vaccine programs were first recommended by Canada's National Advisory Committee on Immunization (NACI) in 2007. In addition to the existing HPV vaccine options in Canada, NACI recently recommended the use of a newly authorized nine-valent HPV (HPV9) vaccine according to a 3-dose immunization schedule for the prevention of HPV types 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52- and 58-related cancers and anogenital warts in females aged 9 to 45 years and males aged 9 to 26 years. New data have emerged evaluating a 2-dose immunization schedule for HPV9 vaccine in males and females, which NACI reviewed in order to provide timely guidance on the possibility of a 2-dose immunization schedule for HPV9 vaccine. Recently, a growing number of studies have also specifically explored the responses of immunocompromised subgroups to HPV vaccines, which also triggered a NACI literature review and updated recommendations on this topic.To review evidence for a 2-dose immunization schedule of the HPV9 vaccine and provide recommendations on vaccine schedule; and to summarize evidence from a recent NACI literature review on the use of HPV vaccines in immunocompromised populations and provide recommendations for HPV vaccine use in these groups.The NACI HPV Working Group reviewed results from a clinical trial of HPV9 vaccine administered with a 2-dose immunization schedule in males and females (protocol V503-010) and performed a literature review on the topic of HPV immunization of immunocompromised populations. The NACI literature review and the NACI statement were published separately.Only one study investigated a 2-dose immunization schedule with HPV9 vaccine, a large manufacturer-sponsored randomized controlled trial (protocol V503-010) of good quality. Taken in context of studies with other HPV vaccines, NACI considered this study to be a sufficient evidence base for recommendations. Through a comprehensive literature review, 27 studies were identified for evidence synthesis including reports on vaccine immunogenicity, safety, or both for immunocompromised populations.Based on the evidence reviewed, NACI issued new recommendations for the use of HPV9 vaccine with a 2-dose immunization schedule at 0, 6-12 months in young females and males and updated the grade of evidence for the use of HPV vaccines in immunocompromised populations.

Project description:BackgroundSafety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons.Methods/designWe will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus.DiscussionGlobally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons.Systematic review registrationPROSPERO CRD42014009794.

Project description:Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effects in vivo following active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, for in vivo evaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized by in vitro assays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growth in vivo was observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.

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Use of licensed vaccines for active immunization of the immunocompromised host.

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Use of licensed vaccines for active immunization of the immunocompromised host.

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