Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation

Datta, Dibyadyuti; Bansal, Gulshan; Gerloff, Dietlind L.; Ellefsen, Barry; Hannaman, Drew; Kumar, Nirbhay

doi:10.1016/j.vaccine.2016.11.072

Cited by 18 publications

(16 citation statements)

References 62 publications

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“…Additionally, none of the other immunogenicity parameters in the combination groups differed from the results obtained with the individual antigens. These results in nonhuman primates and our previous similar findings in mice [17] support the feasibility of combining multiple TBV antigens to improve breadth of immunity and putatively enhance vaccine outcomes.…”

Section: Discussionsupporting

confidence: 85%

“…We have recently reported on immune potency of DNA vaccines encoding Pfs48/45, a lead TBV target antigen, in mice [17], however Pfs48/45 DNA vaccines have not been evaluated in nonhuman primates. We evaluated immunogenicity of glycosylated and unglycosylated forms of Pfs48/45 encoded by DNA vaccines delivered by in vivo EP alone or in combination with Pfs25 in rhesus macaques.…”

Section: Discussionmentioning

confidence: 99%

“…DNA vaccines encoding Pfs25 and Pvs25 (a P. vivax ortholog) have revealed highly potent immunogenicity, especially when administered using in vivo electroporation in mice and nonhuman primates [11–16]. We have recently also reported on induction of transmission-blocking antibodies in mice by DNA vaccine encoding Pfs48/45 [17]. DNA vaccines were first described in the early 1990s and generated much interest due to their simple design, manufacturability, and the ability to induce both cellular and humoral immune responses [18–23].…”

Section: Introductionmentioning

confidence: 99%

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Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques

Datta

Bansal

Grasperge

et al. 2017

Vaccine

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Antibodies recognizing conformational epitopes in Pfs48/45, an antigen expressed on the surface of Plasmodium falciparum gametes and zygotes, have firmly established Pfs48/45 as a promising transmission blocking vaccine (TBV) candidate. However, it has been difficult to reproducibly express Pfs48/45 in a variety of recombinant expression systems. The goal of our studies was to evaluate functional immunogenicity of Pfs48/45 using DNA vaccine format in rhesus macaques. An additional goal was to ensure that when used in combination with another malarial antigen, specific immunity to both antigens was not compromised. For testing combination vaccines, we employed Pfs25 DNA plasmids that have previously undergone evaluations in rodents and nonhuman primates. Pfs25 is expressed on the surface of parasites after fertilization and is also a lead TBV candidate. DNA plasmids based on codon-optimized sequences of Pfs48/45 and Pfs25 were administered by in vivo electroporation, followed by a final recombinant protein boost. Our studies demonstrate that Pfs48/45 encoded by DNA plasmids is capable of inducing potent transmission blocking antibody responses, and such transmission blocking immune potency of Pfs48/45 was not compromised when tested in combination with Pfs25, These findings provide the evidence in favor of further studies on Pfs48/45 and Pfs25, either alone or in combination with other known malaria vaccine candidates for developing effective vaccines capable of interrupting malaria transmission.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques

Datta

Bansal

Grasperge

et al. 2017

Vaccine

Self Cite

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“…The model presented in this paper will still correctly describe the protective efficacy of a combination vaccine based on the actual immune responses generated by each subunit vaccine in the combination formulation, but if antigenic interference has occurred the protective efficacy will fall short of the protection that could have been obtained without antigenic interference. There is still little understanding of the conditions under which antigenic interference occurs; for instance, mixing and co-injecting the vaccines into one site sometimes does [57] and sometimes doesn’t [58] result in antigenic interference, and the same goes for delivery of the component vaccines into separate sites (antigenic interference in some cases, [59], but not in others [60]). If we are to fully exploit the potential of vaccine combination predicted by the model here presented, a thorough study of the conditions under which antigenic interference occurs should be carried out.…”

Section: Discussionmentioning

confidence: 99%

A probabilistic model of pre-erythrocytic malaria vaccine combination in mice

2019

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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 candidates, including TRAP-based vaccines, show no better protective efficacy. This has led to increased interest in combining subunit malaria vaccines as a means of enhancing protective efficacy. Mathematical models of the effect of combining such vaccines on protective efficacy can help inform optimal vaccine strategies and decision-making at all stages of the clinical process. So far, however, no such model has been developed for pre-clinical murine studies, the stage at which all candidate antigens and combinations begin evaluation. To address this gap, this paper develops a mathematical model of vaccine combination adapted to murine malaria studies. The model is based on simple probabilistic assumptions which put the model on a firmer theoretical footing than previous clinical models, which rather than deriving a relationship between immune responses and protective efficacy posit the relationship to be either exponential or Hill curves. Data from pre-clinical murine malaria studies are used to derive values for unknowns in the model which in turn allows simulations of vaccine combination efficacy and suggests optimal strategies to pursue. Finally, the ability of the model to shed light on fundamental biological variables of murine malaria such as the blood stage growth rate and sporozoite infectivity is explored.

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“…During the plasmid design, low-frequency eukaryotic codons in the foreign DNA backbone are identified and replaced for high-frequency codons, while still maintaining their respective coded amino acids [130][131][132]. There has been recent progress in terms of enhancing the immunogenicity in mice and chicken primed with such codon-optimized DNA vaccines [133][134][135].…”

Section: Codon Optimizationmentioning

confidence: 99%

Engineering DNA vaccines against infectious diseases

et al. 2018

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Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. STATEMENT OF SIGNIFICANCE: This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development.

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Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation

Cited by 18 publications

References 62 publications

Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques

Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques

A probabilistic model of pre-erythrocytic malaria vaccine combination in mice

Engineering DNA vaccines against infectious diseases

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