2019
DOI: 10.1371/journal.pone.0209028
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A probabilistic model of pre-erythrocytic malaria vaccine combination in mice

Abstract: Malaria remains one the world’s most deadly infectious diseases, with almost half a million deaths and over 150 million clinical cases each year. An effective vaccine would contribute enormously to malaria control and will almost certainly be required for eventual eradication of the disease. However, the leading malaria vaccine candidate, RTS,S, shows only 30–50% efficacy under field conditions, making it less cost-effective than long-lasting insecticide treated bed nets. Other subunit malaria vaccine candidat… Show more

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Cited by 6 publications
(8 citation statements)
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References 78 publications
(92 reference statements)
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“…Though none of the peptide vaccines in this study shows high levels of protection, the utility of these approaches will be in quickly and reliably discovering new protective B-cell epitopes susceptible to further improvement as parts of highly protective vaccines. The sensitivity of the platform to even low levels of protective efficacy is well-established 11 , and is an advantage of the approach, although variations in (for instance) parasite infectivity between challenge experiments means direct comparison between different experiments is often not possible 20 . The Qβ-peptide platform is also of use for pre-clinical screening of epitopes that will be co-dominant, avoiding antigenic interference, a problem likely to be of increasing importance as single subunit vaccines are replaced by more complex combination strategies 20 22 .…”
Section: Discussionmentioning
confidence: 99%
“…Though none of the peptide vaccines in this study shows high levels of protection, the utility of these approaches will be in quickly and reliably discovering new protective B-cell epitopes susceptible to further improvement as parts of highly protective vaccines. The sensitivity of the platform to even low levels of protective efficacy is well-established 11 , and is an advantage of the approach, although variations in (for instance) parasite infectivity between challenge experiments means direct comparison between different experiments is often not possible 20 . The Qβ-peptide platform is also of use for pre-clinical screening of epitopes that will be co-dominant, avoiding antigenic interference, a problem likely to be of increasing importance as single subunit vaccines are replaced by more complex combination strategies 20 22 .…”
Section: Discussionmentioning
confidence: 99%
“…In theory, two vaccines generating immune responses against different targets will, if either is weakly protective alone, show markedly enhanced efficacy when combined 12 . To test whether “ADGN long” represents a truly novel epitope, rather than its effects being mediated through anti-NANP antibodies as with Qβ-(NANP) 6 , an experiment was carried out combining Qβ-(ADGN long) and Qβ-(NANP) 6 vaccines under suboptimal conditions, with dosage reduced compared to previous experiments (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…To further test whether the enhancement in protective efficacy was consistent with theoretical predictions, a mathematical model developed by our group 12 was adapted to present purposes. From that mathematical model, the following expression can be derived where L V and L N are the numbers of infected hepatocytes in vaccinated and naïve mice, respectively; i V 1 and i V 2 are the reductions in infectivity caused by two different immune components (in this case, against (NANP) 6 and ADGN-long); g is the blood-stage growth rate (calculated in ref.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…In that study soluble full-length P. vivax circumsporozoite protein (PvCSP) was used to vaccinate human volunteers. Low levels of protective efficacy were seen, prompting exploration of alternative strategies [5] , [6] , [7] , [8] . The present study uses a virus-like particle, Qβ, as a platform for eliciting strong antibody responses against PvCSP peptides, followed by challenge of vaccinated mice with transgenic P. berghei parasites expressing the homologous PvCSP protein.…”
Section: Introductionmentioning
confidence: 99%