Correlates of protective immunity following whole sporozoite vaccination against malaria

Doll, Katherine L.; Harty, John T.

doi:10.1007/s12026-014-8525-0

Cited by 35 publications

(29 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent work showed that attenuated sporozoites have to be infectious and invade hepatocytes to unfold their protective potential likely by virtue of expressing new antigens before the cessation of liver stage development. Live sporozoite immunization elicits both protective humoral responses and cellular responses (Doll and Harty 2014). In the 1970s, irradiation-attenuated sporozoites were not considered a practical vaccine because of the issues with irradiation, mass production, preservation, and delivery.…”

Section: Vaccination With Attenuated Preerythrocytic Parasitesmentioning

confidence: 99%

Malaria Parasite Liver Infection and Exoerythrocytic Biology

Vaughan

Kappe

2017

Cold Spring Harb Perspect Med

105

View full text Add to dashboard Cite

In their infection cycle, malaria parasites undergo replication and population expansions within the vertebrate host and the mosquito vector. Host infection initiates with sporozoite invasion of hepatocytes, followed by a dramatic parasite amplification event during liver stage parasite growth and replication within hepatocytes. Each liver stage forms up to 90,000 exoerythrocytic merozoites, which are in turn capable of initiating a blood stage infection. Liver stages not only exploit host hepatocyte resources for nutritional needs but also endeavor to prevent hepatocyte cell death and detection by the host's immune system. Research over the past decade has identified numerous parasite factors that play a critical role during liver infection and has started to delineate a complex web of parasite-host interactions that sustain successful parasite colonization of the mammalian host. Targeting the parasites' obligatory infection of the liver as a gateway to the blood, with drugs and vaccines, constitutes the most effective strategy for malaria eradication, as it would prevent clinical disease and onward transmission of the parasite.

show abstract

Section: Vaccination With Attenuated Preerythrocytic Parasitesmentioning

confidence: 99%

Malaria Parasite Liver Infection and Exoerythrocytic Biology

Vaughan

Kappe

2017

Cold Spring Harb Perspect Med

105

View full text Add to dashboard Cite

show abstract

“…Current vaccines, including those for IAV, do not induce robust T‐cell responses . Developing strategies to induce strong T‐cell memory could improve protection against not only IAV, but also other global health threats including human immunodeficiency virus, tuberculosis, malaria and leishmaniasis against which effective vaccination is currently absent. In the case of IAV, this strategy is supported by human studies correlating more robust CD4 and CD8 T‐cell responses with improved clinical outcomes, and decades of studies in animal models .…”

Section: Introductionmentioning

confidence: 99%

Early programming and late‐acting checkpoints governing the development of CD4 T‐cell memory

Dhume

McKinstry

2018

Immunology

View full text Add to dashboard Cite

CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T-cell generation into vaccine strategies therefore offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin-2, antigen and co-stimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD4 T cells to form memory during two distinct phases of the immune response. First, through 'programming' that occurs during initial priming, and second, through 'checkpoints' that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin-2-, antigen- and co-stimulation-dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD4 T cells.

show abstract

“…In comparison to RAS, this strategy overcomes the problem of fine-tuning irradiation of live parasites as part of a cGMP process, with the advantage that the parasite-based vaccine is also genetically defined and homogenous. However, absolute attenuation of parasites by gene deletion(s) is essential (Doll and Harty, 2014). After the first parasite genes that are only expressed in pre-erythrocytic stages were identified, the first knockout parasites that cause early liver-stage arrest were described in 2005.…”

Section: Genetically Attenuated Parasitesmentioning

confidence: 99%

“…Antibiotics such as azithromycin and clindamycin that prevent development of the parasite apicoplast in the liver stages, leading to liverstage attenuation, also showed highly promising protection in mice (Friesen et al, 2010), as did a single-dose piperaquine regime (Pfeil et al, 2014). Although concerns about drug resistance of parasites, and the practicalities of how to deploy such an immunisation approach, will likely preclude direct mass application of CPS in malaria-endemic areas for now, it is certainly a very valuable tool allowing malaria researchers to better understand underlying immune mechanisms of protection (Doll and Harty, 2014).…”

Section: Infection-treatment Vaccination/chemical Prophylaxis Sporozomentioning

confidence: 99%

“…More recently, de-granulating CD4 þ T cells or cytotoxic CD4 þ T cells were found to be associated with protection against malaria in the CPS-chloroquine clinical trials (Bijker et al, 2014b). In humans, it has been shown that CD4 þ T cell responses are induced, but mechanistic investigation of direct involvement in protection remains extremely difficult (Doll and Harty, 2014).…”

Section: Immune Responses To Wsvmentioning

confidence: 99%

See 1 more Smart Citation