Enhanced CD8+ T Cell Immune Responses and Protection Elicited against <i>Plasmodium berghei</i> Malaria by Prime Boost Immunization Regimens Using a Novel Attenuated Fowlpox Virus

Anderson, Richard; Hannan, Carolyn M.; Gilbert, Sarah C.; Laidlaw, Stephen M.; Sheu, Eric G.; Korten, Simone; Sinden, Robert E.; Butcher, G. A.; Skinner, Michael A.; Hill, Adrian V. S.

doi:10.4049/jimmunol.172.5.3094

Cited by 88 publications

(78 citation statements)

References 41 publications

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“…To both assist evaluating the efficacy of subtype AE regimens suitable for use in Southeast Asia and assess protection across diverse subtypes, we studied four separate subtype AE SHIV vaccine regimens in groups of six macaques (Table 1). We included arms with (i) higher doses on the FPV boost vaccination (based on earlier work with FPV doses in macaques (12), (ii) DNA vaccination only (based on surprisingly good efficacy despite limited immunogenicity with this arm in the previous subtype-B SHIV trial [9]), and (iii) VV prime/FPV boost (based on our own and previous reports demonstrating strong T-cell immunogenicity with this approach [4,23]). The vaccine regimens are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

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Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Rose

Batten

Smith

et al. 2007

J Virol

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Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log 10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.

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Section: Resultsmentioning

confidence: 99%

“…Recent studies suggest that dual poxvirus regimens, such as vaccinia virus (VV) priming and FPV boosting, are highly immunogenic (4,23). Since both are live vector vaccines, a single immunization of each component may suffice.…”

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confidence: 99%

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Rose

Batten

Smith

et al. 2007

J Virol

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“…Protective CD8 T cell immunity against liver-stage Plasmodium infection has been demonstrated after vaccination of rodents with irradiated or genetically attenuated parasites and after subunit vaccination against liver-stage antigens (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Immunity in rodents can last for 6-12 months (3,4,7,13), but in several studies also seems to wane with time (7,(14)(15)(16).…”

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Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria

Schmidt

Podyminogin

Butler

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Infection of mice with sporozoites of Plasmodium berghei or Plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. Unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. Thus, mice may be used better as models to dissect basic parameters required for immunity to Plasmodium-infection than as preclinical vaccine models. In turn, this basic information may aid in the rational design of malaria vaccines. Here, we describe a model of circumsporozoite-specific memory CD8 T cell generation that protects mice against multiple P. berghei sporozoite challenges for at least 19 months. Using this model we defined a threshold frequency of memory CD8 T cells in the blood that predicts long-term sterilizing immunity against liver-stage infection. Importantly, the number of Plasmodium-specific memory CD8 T cells required for immunity greatly exceeds the number required for resistance to other pathogens. In addition, this model allowed us to identify readily individual immunized mice that exceed or fall below the protective threshold before infection, information that should greatly facilitate studies to dissect basic mechanisms of protective CD8 T cell memory against liver-stage Plasmodium infection. Furthermore, the extremely large threshold in memory CD8 T cell frequencies required for long-term protection in mice may have important implications for development of effective malaria vaccines.

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“…Sterile protection against sporozoite challenge can be transferred to naïve mice by CSP-specific CD8 + T cells [15][16][17][18]. There are several experimental vaccines described that successfully induce CSP-specific CD8 + T cells [19][20][21][22].In the present study we employed our previously described heterologous prime/boost vaccination strategy that is based on the induction of CD8 + T cells recognising a CSP-derived epitope of Plasmodium berghei presented by MHC class I [23]. Primary immunization is achieved with recombinant Salmonella.…”

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Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8⁺ memory T cells

et al. 2013

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Protection against malaria can be achieved by induction of a strong CD8 + T-cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long-lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8 + T-cell response and sterile protection, which is short-lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite-specific antibodies that showed protective capacity. The numbers of CSP-specific CD8 + T cells were not substantially enhanced by sporozoite infections; however, CSP-specific memory CD8 + T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized-only mice. CD4 + T cells contributed to protection as well; but CD8 + memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8 + effector-memory T cells with increased cytotoxic activity as well as CD4 + memory T cells and neutralizing antibodies. Keywords: CD8 + T cells r Plasmodium r Sporozoites r VaccinationAdditional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Susanne Tartz e-mail: tartz@bni-hamburg.de IntroductionThere is now good progress both in the prevention and the treatment of malaria that leads to decreasing numbers of malaria cases and fatalities; nevertheless malaria is still one of the biggest C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 694Susanne Tartz et al. Eur. J. Immunol. 2013. 43: 693-704 challenges for global public health management. There are around 250 million cases per year worldwide with the vast majority of these in the African region and it is estimated that malaria accounts for 900 000 deaths annually [1]. Therefore a vaccine is still the ultimate goal of malaria research. The development of immunity and immunological memory to Plasmodium infections in malaria endemic areas has been intensively studied [2]. Children in the age of 6 months to 5 years are at the highest risk of being infected with Plasmodium and developing severe disease. In the first years of life, an anti-disease immunity is acquired that leads to high-density infections with mild symptoms. In contrast, the acquisition of anti-parasite immunity takes years to decades, although transmigrant studies show that adults may acquire immunity more rapidly than children [3,4]. It is supposed that anti-parasite immunity is based mainly on antibodies recognising variant surface antigens on the membranes of infected erythrocytes whereas immune responses against preerythrocytic forms seem to play a m...

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Enhanced CD8+ T Cell Immune Responses and Protection Elicited against Plasmodium berghei Malaria by Prime Boost Immunization Regimens Using a Novel Attenuated Fowlpox Virus

Cited by 88 publications

References 41 publications

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria

Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8⁺ memory T cells

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Enhanced CD8+ T Cell Immune Responses and Protection Elicited against Plasmodium berghei Malaria by Prime Boost Immunization Regimens Using a Novel Attenuated Fowlpox Virus

Cited by 88 publications

References 41 publications

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria

Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8+ memory T cells

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Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8⁺ memory T cells