Genetic diversity-independent neutralization of pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1 strain of influenza) and carcinogenic (e.g. HBV and HCV) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (EVNCs).
ABSTRACT Genetic diversity and hypermutation contribute to difficulties in developing a vaccine against viruses like HIV and influenza. There are currently no known immune correlates of protection against HIV. This has made the development of a vaccine against HIV that would provide sterilizing immunity in the near future an impossible task. The abandonment of a recent AIDS vaccine human trial due to a failure to elicit a protective sterilising immune response confirms that empirical attempts to develop a vaccine may result in failures. Also the difficulty in predicting the next pandemic strain of influenza may make it difficult to respond rapidly should there be an outbreak. Therefore, it is time to explore broad spectrum agents that can target either the lipid portion of the envelope or the sugar moieties of the glycoproteins or the rafts (regions within viral and cell envelopes where a higher concentration of the glycoproteins exist). Broad spectrum agents that can serve as disrafters or neutralize the viral infectivity by binding to the envelope lipid or sugar moieties will not be affected by the vagaries of hypermutation of surface antigens. This is because the post-translation modification is a host function. Presented here is a review of recently reported agents present in pomegranate juice (polyphenols, beta-sitosterol, sugars and ellagic acid) and fulvic acid, described here as the envelope virus neutralising compounds (EVNCs) and complex molecules like lectins and mucins. Pomegranate juice was previously reported to inactivate HIV and further shown by our group to inactivate influenza, herpes viruses and poxviruses. A formulation consisting of fulvic acid, a complex mixture of compounds was previously reported to render vaccinia virus, HIV and SARS virus non-infectious. Recently, both fulvic acid and pomegranate juice have been shown to inactivate genetically diverse strains of influenza including H5N1, further confirming the broad spectrum nature of these agents. How EVNCs will be used in developing a vaccine achieving sterilizing immunity or prophylaxis needs to be researched.
SourceAvailable from: Cassandra M Berry[Show abstract] [Hide abstract]
ABSTRACT: Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.01/2014; 2014:267594. DOI:10.1155/2014/267594
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ABSTRACT: Human norovirus is the leading cause of sporadic gastroenteritis, which is responsible for more than 90% of all non-bacterial gastroenteritis outbreaks. While norovirus infections typically cause mild and self-limiting symptoms lasting 24–48 h, chronic persistent infections can cause severe symptoms. Although recent advances have been made in understanding the molecular characteristics of norovirus infection, no norovirus-specific antiviral drugs or vaccines are available. Conventional intervention methods used to inactivate norovirus, such as treatment with disinfecting agents (e.g., ethanol, hypochlorite, and quaternary ammonium formulations), have shown a lack of efficacy against human norovirus when they are applied to foods and in food preparation processes. Therefore, alternative antiviral or inactivating agents such as phytochemicals have received attention as potential norovirus inhibitors due to their relatively low toxicity and lack of side effects, which allows them to be prepared as food-safe formulations. Evidence from studies using viral surrogates suggests that numerous phytochemicals and foods containing flavonoids and polyphenols have anti-norovirus activity, and future studies will be necessary to confirm the effectiveness of such compounds against human norovirus and the molecular mechanisms through which they produce antiviral effects.This article is protected by copyright. All rights reservedMolecular Nutrition & Food Research 01/2015; 59(1). DOI:10.1002/mnfr.201400549 · 4.91 Impact Factor
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ABSTRACT: Vaccine development for viral diseases is a challenge where subunit vaccines are often ineffective. Therefore, the need for alternative solutions is crucial. Thus, short peptide vaccine candidates promise effective answers under such circumstances. Short peptide vaccine candidates are linear T-cell epitopes (antigenic determinants that are recognized by the immune system) that specifically function by binding human leukocyte antigen (HLA) alleles of different ethnicities (including Black, Caucasian, Oriental, Hispanic, Pacific Islander, American Indian, Australian aboriginal, and mixed ethnicities). The population specific allele level HLA sequence data in the public IMGT/HLA database contains approximately 11,000 nomenclature defined class I (8,576) and class II (2,649) HLA alleles as of May, 2014 present in several ethnic populations. The bottleneck in short peptide vaccine design and development is HLA polymorphism on the one hand and viral diversity on the other hand. Hence, a crucial step in its design and development is HLA allele specific binding of short antigen peptides. This is usually combinatorial and computationally labor intensive. Mathematical models utilizing structure-defined pockets are currently available for class I and class II HLA-peptide binding peptides. Frameworks have been developed to design protocols to identify the most feasible short peptide cocktails as vaccine candidates with super-antigen properties among known HLA super-types. This approach is a promising solution to develop new viral vaccines given the current advancement in T-cell immuno-informatics, yet challenging in terms of prediction efficiency and protocol development.Short peptide vaccine design: Promises and Challenges, 1 12/2014; SPRINGER, New York, USA.