Vaccines: Correlates of Vaccine‐Induced Immunity

Sanofi Pasteur, Doylestown, Pennsylvania, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 08/2008; 47(3):401-9. DOI: 10.1086/589862
Source: PubMed


The immune system is redundant, and B and T cells collaborate. However, almost all current vaccines work through induction of antibodies in serum or on mucosa that block infection or interfere with microbial invasion of the bloodstream. To protect, antibodies must be functional in the sense of neutralization or opsonophagocytosis. Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors. There may be >1 correlate of protection for a disease, which we term "cocorrelates." Either effector or central memory may correlate with protection. Cell-mediated immunity also may operate as a correlate or cocorrelate of protection against disease, rather than against infection. In situations where the true correlate of protection is unknown or difficult to measure, surrogate tests (usually antibody measurements) must suffice as predictors of protection by vaccines. Examples of each circumstance are given.

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    • "As reviewed by Plotkin (2008), a correlate of protection is defined as " a specific immune response to a vaccine that is closely related to protection against infection, disease, or other defined end point " ( p. 402). Correlates of protection may be absolute (i.e., near complete) or relative (i.e., partial) and may involve multiple synergistic components (i.e., co-correlates). "
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    ABSTRACT: Tuberculosis (TB) is a premier example of a disease complex with pathogens primarily affecting humans (i.e., Mycobacterium tuberculosis) or livestock and wildlife (i.e., Mycobacterium bovis) and with a long history of inclusive collaborations between physicians and veterinarians. Advances in the study of bovine TB have been applied to human TB, and vice versa. For instance, landmark discoveries on the use of Koch's tuberculin and interferon-γ release assays for diagnostic purposes, as well as Calmette and Guérin's attenuated M. bovis strain as a vaccine, were first evaluated in cattle for control of bovine TB prior to wide-scale use in humans. Likewise, recent discoveries on the role of effector/memory T cell subsets and polyfunctional T cells in the immune response to human TB, particularly as related to vaccine efficacy, have paved the way for similar studies in cattle. Over the past 15 years, substantial funding for development of human TB vaccines has led to the emergence of multiple promising candidates now in human clinical trials. Several of these vaccines are being tested for immunogenicity and efficacy in cattle. Also, the development of population-based vaccination strategies for control of M. bovis infection in wildlife reservoirs will undoubtedly have an impact on our understanding of herd immunity with relevance to the control of both bovine and human TB in regions of the world with high prevalence of TB. Thus, the one-health approach to research on TB is mutually beneficial for our understanding and control of TB in humans, livestock, and wildlife. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 05/2015; 56(1):26-43. DOI:10.1093/ilar/ilv001 · 2.39 Impact Factor
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    • "Hence cytokine profiling for immunological monitoring of T-cell responses are best studied by stimulating Tcells in vitro in an antigen specific manner and then analysing the patterns of cytokine induction at mRNA or protein level using various assays, so called antigen-specific cytokine responses. The antigen-specific cytokine response is likely to be an important part of vaccine assessment [9] [10] [11] and can be used to monitor immune status of animals during disease progression or following vaccination. "
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    ABSTRACT: The interest in analysing antigen-specific cytokine responses has substantially increased in recent years, in part due to their use in assessing vaccine efficacy. In the present study, the kinetics of IL-2, IL-4 and IFN-γ expression was determined in bovine PBMCs by real-time PCR and in whole blood by cytokine-release assay after in vitro stimulation with recall foot-and-mouth disease virus (FMDV) antigen. The results showed that the cytokine mRNA of IL-2 and IFN-γ in PBMCs were induced early (peak induction at 6 h), whereas the IL-4 mRNA showed delayed induction (peaked at 24 h). In contrast, the kinetics of cytokine proteins in whole blood was different and required the accumulation of the proteins before being optimally detected. The peak accumulation of cytokine protein in whole blood was recorded at 72 h for IL-2 and IL-4, and 96 h for IFN-γ. The findings of this study are of importance when selecting an optimal time points for measuring antigen-specific cytokine expression in cattle.
    Cytokine 03/2015; 72(1):58–62. DOI:10.1016/j.cyto.2014.12.011 · 2.66 Impact Factor
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    • "Only 50% of the vaccinated cats strongly neutralised the pseudotype bearing KKS Env, the sequence of which closely resembles that of FIV-Petaluma [33], one component of the divalent FIV vaccine [21]. A strong NAb response had been proposed as a correlate of protection [46] [47] and a crucial component of humoral immunity against virus infections [48] [49]. Initial studies reported that NAbs recognising the homologous Petaluma and Shizuoka strains were detected in most vaccinated cats and eight of twelve vaccinated cats neutralised the heterologous FIV Bangston isolate, leading to the conclusion that the two isolates of FIV within the vaccine might act synergistically to enhance the development of NAbs against heterologous strains of FIV [2]. "
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    ABSTRACT: Across human and veterinary medicine, vaccines against only two retroviral infections have been brought to market successfully, the vaccines against feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). FeLV vaccines have been a global success story, reducing virus prevalence in countries where uptake is high. In contrast, the more recent FIV vaccine was introduced in 2002 and the degree of protection afforded in the field remains to be established. However, given the similarities between FIV and HIV, field studies of FIV vaccine efficacy are likely to advise and inform the development of future approaches to HIV vaccination. Here we assessed the neutralising antibody response induced by FIV vaccination against a panel of FIV isolates, by testing blood samples collected from client-owned vaccinated Australian cats. We examined the molecular and phenotypic properties of 24 envs isolated from one vaccinated cat that we speculated might have become infected following natural exposure to FIV. Cats vaccinated against FIV did not display broadly neutralising antibodies, suggesting that protection may not extend to some virulent recombinant strains of FIV circulating in Australia. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 01/2015; 11(8). DOI:10.1016/j.vaccine.2015.01.028 · 3.62 Impact Factor
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