Research

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15 pages, 2773 KiB

Open AccessArticle

Engineering Antigens to Assemble into Polymer Particle Vaccines for Prevention of Streptococcus suis Infection

by Zennia Jean C. Gonzaga, Shuxiong Chen, Mélanie Lehoux, Mariela Segura and Bernd H. A. Rehm

Vaccines 2021, 9(12), 1386; https://doi.org/10.3390/vaccines9121386 - 24 Nov 2021

Cited by 3 | Viewed by 2192

Streptococcus suis is a zoonotic pathogen affecting pigs and humans. This bacterium causes severe economic losses in the swine industry and poses a serious threat to public health and food safety. There is no effective commercial vaccine available for pigs or humans. In [...] Read more.

Streptococcus suis is a zoonotic pathogen affecting pigs and humans. This bacterium causes severe economic losses in the swine industry and poses a serious threat to public health and food safety. There is no effective commercial vaccine available for pigs or humans. In this study, we applied the biopolymer particle (BP) vaccine technology to incorporate seven conserved S. suis antigens (38 kDa protein (38), enolase (Enol), SSU1915, SSU1355, SSU0185, SSU1215, and SSU1773 (SSU1 and SSU2)). Two combinations of these antigens (38 and Enol; all SSU antigens designated as SSU1 and SSU2) were engineered to mediate production of BPs coated with either antigens 38 and Enol or SSU1 and SSU2 inside recombinant Escherichia coli. The isolated and purified empty BPs, 38-BP-Enol and SSU1-BP-SSU2, showed size ranges of 312–428 nm and 292–344 nm with and without the QuilA^® adjuvant, respectively, and all showed a negative surface charge. Further characterization of purified BPs confirmed the presence of the expected antigen-comprising fusion proteins as assessed by tryptic peptide fingerprinting analysis using quadrupole time-of-flight mass spectrometry and immunoblotting. Vaccination with 38-BP-Enol and SSU1-BP-SSU2 formulated with and without QuilA^® adjuvant induced significant antigen-specific humoral immune responses in mice. Antigen-coated BPs induced significant and specific Ig (IgM + IgG) and IgG immune responses (1.0 × 10⁶–1.0 × 10⁷) when compared with mice vaccinated with empty BPs. Functionality of the immune response was confirmed in challenge experiments using an acute murine S. suis infection model, which showed 100% survival of the 38-BP-Enol and SSU1-BP-SSU2 vaccinated mice compared to 70% survival when vaccinated with empty BPs. Overall, our data suggest that S. suis antigen-coated BPs could be developed into particulate vaccines that induce protective immunity against S. suis infections. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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15 pages, 4573 KiB

Open AccessArticle

An Advax-Adjuvanted Inactivated Cell-Culture Derived Japanese Encephalitis Vaccine Induces Broadly Neutralising Anti-Flavivirus Antibodies, Robust Cellular Immunity and Provides Single Dose Protection

by Tomoyoshi Komiya, Yoshikazu Honda-Okubo, Jeremy Baldwin and Nikolai Petrovsky

Vaccines 2021, 9(11), 1235; https://doi.org/10.3390/vaccines9111235 - 23 Oct 2021

Cited by 10 | Viewed by 2561

Abstract

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of [...] Read more.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE+Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley encephalitis virus (MVEV), St Louis encephalitis virus (SLEV) and Dengue virus-1 and -2 (DENV-1 and -2). Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody-dependent infection enhancement (ADIE) activity, in contrast to high ADIE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. In a mouse lethal challenge study against highly virulent JaTH160 JEV strain, ccJE+Advax conferred complete protection in a two-dose schedule with 50 ng of vaccine antigen and near complete protection after a single 200 ng dose of vaccine antigen. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLEV and MVEV. Given its ability to provide single-dose JEV protection and induce broadly neutralising antibodies devoid of ADIE activity, ccJE+Advax vaccine could be useful in situations where rapid protection is desirable, e.g., during a local outbreak or for use in travellers or armies requiring rapid deployment to JEV endemic regions. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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16 pages, 5519 KiB

Open AccessArticle

Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

by Ahmed O. Shalash, Luke Becker, Jieru Yang, Paul Giacomin, Mark Pearson, Waleed M. Hussein, Alex Loukas, Mariusz Skwarczynski and Istvan Toth

Vaccines 2021, 9(9), 1034; https://doi.org/10.3390/vaccines9091034 - 17 Sep 2021

Cited by 15 | Viewed by 3553

Abstract

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass [...] Read more.

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL₁₀ or LL₁₀, respectively) groups as self-adjuvanting moieties. BL₁₀ and LL₁₀ induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL₁₀. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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15 pages, 2764 KiB

Open AccessArticle

Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate

by Jeffrey Seow, Sreedam C. Das, Rodrigo A. V. Morales, Ricardo Ataide, Bankala Krishnarjuna, Mitchell Silk, David K. Chalmers, Jack Richards, Robin F. Anders, Christopher A. MacRaild and Raymond S. Norton

Vaccines 2021, 9(8), 855; https://doi.org/10.3390/vaccines9080855 - 04 Aug 2021

Cited by 2 | Viewed by 2192

Abstract

The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass [...] Read more.

The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass the hurdle of strain-specificity is to bias the immune response towards the conserved regions. Two mouse monoclonal antibodies, 4D11 and 9H4, recognise the conserved C-terminal region of MSP2. Although they bind overlapping epitopes, 4D11 reacts more strongly with native MSP2, suggesting that its epitope is more accessible on the parasite surface. In this study, a structure-based vaccine design approach was applied to the intrinsically disordered antigen, MSP2, using a crystal structure of 4D11 Fv in complex with its minimal binding epitope. Molecular dynamics simulations and surface plasmon resonance informed the design of a series of constrained peptides that mimicked the 4D11-bound epitope structure. These peptides were conjugated to keyhole limpet hemocyanin and used to immunise mice, with high to moderate antibody titres being generated in all groups. The specificities of antibody responses revealed that a single point mutation can focus the antibody response towards a more favourable epitope. This structure-based approach to peptide vaccine design may be useful not only for MSP2-based malaria vaccines, but also for other intrinsically disordered antigens. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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20 pages, 2584 KiB

Open AccessArticle

A Pseudomonas aeruginosa-Derived Particulate Vaccine Protects against P. aeruginosa Infection

by Zennia Jean C. Gonzaga, Christina Merakou, Antonio DiGiandomenico, Gregory P. Priebe and Bernd H. A. Rehm

Vaccines 2021, 9(7), 803; https://doi.org/10.3390/vaccines9070803 - 20 Jul 2021

Cited by 14 | Viewed by 4153

Abstract

Despite numerous efforts to develop an effective vaccine against Pseudomonas aeruginosa, no vaccine has yet been approved for human use. This study investigates the utility of the P. aeruginosa inherently produced polyhydroxyalkanaote (PHA) inclusions and associated host–cell proteins (HCP) as a [...] Read more.

Despite numerous efforts to develop an effective vaccine against Pseudomonas aeruginosa, no vaccine has yet been approved for human use. This study investigates the utility of the P. aeruginosa inherently produced polyhydroxyalkanaote (PHA) inclusions and associated host–cell proteins (HCP) as a particulate vaccine platform. We further engineered PHA inclusions to display epitopes derived from the outer membrane proteins OprF/OprI/AlgE (Ag) or the type III secretion system translocator PopB. PHA and engineered PHA beads induced antigen-specific humoral, cell-mediated immune responses, anti-HCP and anti-polysaccharide Psl responses in mice. Antibodies mediated opsonophagocytic killing and serotype-independent protective immunity as shown by 100% survival upon challenge with P. aeruginosa in an acute pneumonia murine model. Vaccines were stable at 4 °C for at least one year. Overall, our data suggest that vaccination with subcellular empty PHA beads was sufficient to elicit multiple immune effectors that can prevent P. aeruginosa infection. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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Review

Jump to: Research

19 pages, 1201 KiB

Open AccessReview

Chimeric Vaccines Based on Novel Insect-Specific Flaviviruses

by Jessica J. Harrison, Jody Hobson-Peters, Helle Bielefeldt-Ohmann and Roy A. Hall

Vaccines 2021, 9(11), 1230; https://doi.org/10.3390/vaccines9111230 - 22 Oct 2021

Cited by 11 | Viewed by 3219

Abstract

Vector-borne flaviviruses are responsible for nearly half a billion human infections worldwide each year, resulting in millions of cases of debilitating and severe diseases and approximately 115,000 deaths. While approved vaccines are available for some of these viruses, the ongoing efficacy, safety and [...] Read more.

Vector-borne flaviviruses are responsible for nearly half a billion human infections worldwide each year, resulting in millions of cases of debilitating and severe diseases and approximately 115,000 deaths. While approved vaccines are available for some of these viruses, the ongoing efficacy, safety and supply of these vaccines are still a significant problem. New technologies that address these issues and ideally allow for the safe and economical manufacture of vaccines in resource-poor countries where flavivirus vaccines are in most demand are urgently required. Preferably a new vaccine platform would be broadly applicable to all flavivirus diseases and provide new candidate vaccines for those diseases not yet covered, as well as the flexibility to rapidly pivot to respond to newly emerged flavivirus diseases. Here, we review studies conducted on novel chimeric vaccines derived from insect-specific flaviviruses that provide a potentially safe and simple system to produce highly effective vaccines against a broad spectrum of flavivirus diseases. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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13 pages, 314 KiB

Open AccessFeature PaperReview

A Review of Australian Tick Vaccine Research

by Ala E. Tabor

Vaccines 2021, 9(9), 1030; https://doi.org/10.3390/vaccines9091030 - 16 Sep 2021

Cited by 15 | Viewed by 3315

Abstract

Tick vaccine research in Australia has demonstrated leadership worldwide through the development of the first anti-tick vaccine in the 1990s. Australia’s Commonwealth Scientific and Industrial Research Organisation’s (CSIRO) research led to the development of vaccines and/or precursors of vaccines (such as crude extracts) [...] Read more.

Tick vaccine research in Australia has demonstrated leadership worldwide through the development of the first anti-tick vaccine in the 1990s. Australia’s Commonwealth Scientific and Industrial Research Organisation’s (CSIRO) research led to the development of vaccines and/or precursors of vaccines (such as crude extracts) for both the cattle tick and the paralysis tick. CSIRO commercialised the Bm86 vaccine in the early 1990s for Rhipicephalus australis; however, issues with dosing and lack of global conservation led to the market closure of Tick-GARD in Australia. New research programs arose both locally and globally. The Australian paralysis tick Ixodes holocyclus has perplexed research veterinarians since the 1920s; however, not until the 2000s did biotechnology exist to elucidate the neurotoxin—holocyclotoxin family of toxins leading to a proof of concept vaccine cocktail. This review revisits these discoveries and describes tributes to deceased tick vaccine protagonists in Australia, including Sir Clunies Ross, Dr Bernard Stone and Dr David Kemp. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

19 pages, 329 KiB

Open AccessReview

Australia’s Role in Pneumococcal and Human Papillomavirus Vaccine Evaluation in Asia-Pacific

by Zheng Quan Toh, Chau Quang, Joseph A. Tooma, Suzanne M. Garland, Kim Mulholland and Paul V. Licciardi

Vaccines 2021, 9(8), 921; https://doi.org/10.3390/vaccines9080921 - 18 Aug 2021

Viewed by 2225

Abstract

Australian researchers have made substantial contributions to the field of vaccinology over many decades. Two examples of this contribution relate to pneumococcal vaccines and the human papillomavirus (HPV) vaccine, with a focus on improving access to these vaccines in low- and lower-middle-income countries [...] Read more.

Australian researchers have made substantial contributions to the field of vaccinology over many decades. Two examples of this contribution relate to pneumococcal vaccines and the human papillomavirus (HPV) vaccine, with a focus on improving access to these vaccines in low- and lower-middle-income countries (LLMICs). Many LLMICs considering introducing one or both of these vaccines into their National Immunisation Programs face significant barriers such as cost, logistics associated with vaccine delivery. These countries also often lack the resources and expertise to undertake the necessary studies to evaluate vaccine performance. This review summarizes the role of Australia in the development and/or evaluation of pneumococcal vaccines and the HPV vaccine, including the use of alternative vaccine strategies among countries situated in the Asia-Pacific region. The outcomes of these research programs have had significant global health impacts, highlighting the importance of these vaccines in preventing pneumococcal disease as well as HPV-associated diseases. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

14 pages, 310 KiB

Open AccessReview

The Search for a Schistosomiasis Vaccine: Australia’s Contribution

by Donald P. McManus

Vaccines 2021, 9(8), 872; https://doi.org/10.3390/vaccines9080872 - 06 Aug 2021

Cited by 7 | Viewed by 2696

Abstract

Schistosomiasis, a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, results in considerable human morbidity in sub-Saharan Africa, in particular, but also parts of the Middle East, South America, and Southeast Asia. The anti-schistosome drug praziquantel is efficacious and [...] Read more.

Schistosomiasis, a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, results in considerable human morbidity in sub-Saharan Africa, in particular, but also parts of the Middle East, South America, and Southeast Asia. The anti-schistosome drug praziquantel is efficacious and safe against the adult parasites of all Schistosoma species infecting humans; however, it does not prevent reinfection and the development of drug resistance is a constant concern. The need to develop an effective vaccine is of great importance if the health of many in the developing world is to be improved. Indeed, vaccination, in combination with other public health measures, can provide an invaluable tool to achieve lasting control, leading to schistosomiasis elimination. Australia has played a leading role in schistosomiasis vaccine research over many years and this review presents an overview of some of the significant contributions made by Australian scientists in this important area. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

16 pages, 6325 KiB

Open AccessReview

Vaccine Candidates for the Control and Prevention of the Sexually Transmitted Disease Gonorrhea

by Ethan C. Haese, Van C. Thai and Charlene M. Kahler

Vaccines 2021, 9(7), 804; https://doi.org/10.3390/vaccines9070804 - 20 Jul 2021

Cited by 13 | Viewed by 9201

Abstract

The World Health Organization (WHO) has placed N. gonorrhoeae on the global priority list of antimicrobial resistant pathogens and is urgently seeking the development of new intervention strategies. N. gonorrhoeae causes 86.9 million cases globally per annum. The effects of gonococcal disease are [...] Read more.

The World Health Organization (WHO) has placed N. gonorrhoeae on the global priority list of antimicrobial resistant pathogens and is urgently seeking the development of new intervention strategies. N. gonorrhoeae causes 86.9 million cases globally per annum. The effects of gonococcal disease are seen predominantly in women and children and especially in the Australian Indigenous community. While economic modelling suggests that this infection alone may directly cost the USA health care system USD 11.0–20.6 billion, indirect costs associated with adverse disease and pregnancy outcomes, disease prevention, and productivity loss, mean that the overall effect of the disease is far greater still. In this review, we summate the current progress towards the development of a gonorrhea vaccine and describe the clinical trials being undertaken in Australia to assess the efficacy of the current formulation of Bexsero^® in controlling disease. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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29 pages, 13825 KiB

Open AccessReview

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

by Thai Thanh Hoang Thi, Estelle J. A. Suys, Jung Seok Lee, Dai Hai Nguyen, Ki Dong Park and Nghia P. Truong

Vaccines 2021, 9(4), 359; https://doi.org/10.3390/vaccines9040359 - 08 Apr 2021

Cited by 234 | Viewed by 22776

Abstract

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil^® [...] Read more.

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil^® and Onpattro^®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies. Full article

(This article belongs to the Special Issue Vaccines Development in Australia)

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