Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice

Shollenberger, Lisa M.; Bui, Cac T.; Paterson, Yvonne; Allen, Kelsey; Harn, Donald A.

doi:10.1016/j.vaccine.2013.02.037

Cited by 9 publications

(8 citation statements)

References 44 publications

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“…Despite the limits of murine models to reflect every aspect of the human situation, combined evidence gained in different mouse models for helminth infection can be informative. Since first murine studies demonstrated successful vaccination despite concurrent nematode infection by improved vaccination strategies [21], [30], [59], [60], we suggest that development of vaccination regimes that are functional despite pre-existing nematode infection would be more promising and should be considered in addition to deworming programs before vaccination.…”

Section: Discussionmentioning

confidence: 99%

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

2014

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One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections.

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Section: Discussionmentioning

confidence: 99%

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

2014

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“…Although it is well known that Listeria is a potent inducer of CD8 ϩ immunity, the specific mechanism(s) by which Listeria vector vaccines can both overcome the immunosuppressive environment of chronic helminth infection (12,13) as well as be adjuvanted by SEA is currently being investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Helminth parasites bias immune responses to the CD4 ϩ Th2 type and can be immune suppressive (3)(4)(5)(6)(7)(8)(9)(10). To evaluate the influence of helminth infection on vaccines, we can evaluate the ability to induce vaccine-specific immune responses in helminth-infected recipients or in recipients who have been treated with immune-biasing helminth antigens (11)(12)(13).…”

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confidence: 99%

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Schistosoma mansoni Soluble Egg Antigens Enhance T Cell Responses to a Newly Identified HIV-1 Gag H-2^bEpitope

Bui

Shollenberger

Paterson

et al. 2014

Clin. Vaccine Immunol.

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c Schistosome infection induces significant T helper type 2 (Th2) and anti-inflammatory immune responses and has been shown to negatively impact vaccine efficacy. Our goal was to determine if the administration of schistosome soluble egg antigens (SEA) would negatively influence the induction of cytotoxic T lymphocyte (CTL) and Th1-type T cell responses to an HIV candidate vaccine in the Th1-biased C57BL/6 mouse strain. Initial experiments failed, as we were unable to detect any response to the defined class I epitope for HIV-1 IIIB Gag. Therefore, we initiated an epitope mapping study to identify C57BL/6 (H-2 b ) T cell epitopes in HIV-1 IIIB Gag in order to perform the experiments. This analysis defined two previously unreported minimal class I H-2 b and class II I-A b epitopes for HIV-1 IIIB Gag. The newly defined HIV-1 IIIB Gag epitopes were used to evaluate the influence of SEA on the generation of CTL and Th1-type HIV-1 IIIB Gag responses. Surprisingly, in contrast to our hypothesis, we observed that the coadministration of SEA with a Listeria monocytogenes vector expressing HIV-1 IIIB Gag (Lm-Gag) led to a significantly increased frequency of gamma interferon (IFN-␥)-producing CD8؉ and CD4 ؉ T cells in C57BL/6 mice compared to mice immunized with Lm-Gag only. These observations suggest that SEA contains, in addition to Th2-type and immune-suppressive molecules, substances that can act with the Lm-Gag vaccine to increase CTL and Th1-type vaccine-specific immune responses.V accines for human immunodeficiency virus (HIV), tuberculosis, and malaria are in development or in clinical trials. The greatest incidence of each of these diseases is in sub-Saharan Africa, where helminth infection is endemic (1, 2). Helminth parasites bias immune responses to the CD4 ϩ Th2 type and can be immune suppressive (3-10). To evaluate the influence of helminth infection on vaccines, we can evaluate the ability to induce vaccine-specific immune responses in helminth-infected recipients or in recipients who have been treated with immune-biasing helminth antigens (11-13).Schistosomiasis is a helminth parasitic disease that affects Ͼ200 million people worldwide and is listed by the World Health Organization (WHO) as the second leading parasitic disease, after malaria (14). Infection occurs when cercariae that emerge from infected snail intermediate hosts contact and penetrate the skin of the vertebrate host. Larval parasites migrate and mature into adult male and female worms that mate and produce eggs (4, 6). Eggs that become lodged within host tissues are largely responsible for Th2 biasing of the host immune system and induction of antiinflammatory responses (3,4,6,15,16).Immune biasing induced by schistosome infection has been shown to reduce vaccine efficacy in both laboratory and clinical settings (8,11,17,18). Specifically, helminth infection has been shown to suppress immune responses to a Th1-type vaccine and impair the expansion of pathogen-specific cytotoxic CD8ϩ T cell (cytotoxic T lymphocyte [CTL]) responses (18)(19)(...

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“…25,26 Lm-based vaccination has also succeeded in inducing robust and functional HIV-specific cellular immune responses in mice regardless of underlying chronic infection status (e.g., helminth infections). 27 Against the parasite Leishmania major, immunization of mice with recombinant Lm delivering an L. major antigen has been shown to generate in vivo CD4 + T cells with a Th1 phenotype that exerted protective antiparasitic function. 28 Lastly, a recombinant Lm vaccine stably expressing the IglC protein of Francisella tularensis was found to induce protective immunity against lethal F. tularensis challenge in mice; this success was shown to be due to the powerful cellular CD4 + and CD8 + T cell immune responses against IglC.…”

Section: Anti-tumor Lm-based Immunotherapymentioning

confidence: 99%

Listeria monocytogenes

Liang

Sherrid

Wallecha

et al. 2014

Human Vaccines & Immunotherapeutics

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Vaccination as a medical intervention has proven capable of greatly reducing the suffering from childhood infectious disease. However, newborns and infants in particular are age groups for whom adequate vaccine-mediated protection is still largely lacking. With the challenges that the neonatal immune system faces and the required highest level of stringency for safety, designing vaccines for early life in general and the newborn in particular poses great difficulty. Nevertheless, recent advances in our understanding of neonatal immunity and its responses to vaccines and adjuvants suggest that neonatal vaccination is a task fully within reach. Among the most promising developments in neonatal vaccination is the use of Listeria monocytogenes (Lm) as a delivery platform. In this review, we will outline key properties of Lm that make it such an ideal neonatal and early life vaccine vehicle, and also discuss potential constraints of Lm as a vaccine delivery platform.

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Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice

Cited by 9 publications

References 44 publications

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Schistosoma mansoni Soluble Egg Antigens Enhance T Cell Responses to a Newly Identified HIV-1 Gag H-2^bEpitope

Listeria monocytogenes

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Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice

Cited by 9 publications

References 44 publications

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Schistosoma mansoni Soluble Egg Antigens Enhance T Cell Responses to a Newly Identified HIV-1 Gag H-2bEpitope

Listeria monocytogenes

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Schistosoma mansoni Soluble Egg Antigens Enhance T Cell Responses to a Newly Identified HIV-1 Gag H-2^bEpitope