Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

Delrue, Iris; Verzele, Dieter; Madder, Annemieke; Nauwynck, Hans

doi:10.1586/erv.12.38

Cited by 162 publications

(175 citation statements)

References 98 publications

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“…In addition, inactivated viruses are often used for vaccine development. However, the challenge in using inactivated viruses as vaccines relies on the need to inactivate viruses completely to make them safe while simultaneously preserving intact the viral epitopes that give rise to protective immune responses (79,80). The rapid Raman spectroscopy technology developed in our study thus has the potential of assisting in the characterization of inactivated viruses for vaccine development.…”

Section: Discussionmentioning

confidence: 99%

Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy

Liu

Benavides-Montaño

et al. 2013

J Virol

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Conformational changes in the glycoproteins of enveloped viruses are essential for membrane fusion, a critical step during both viral entry and the pathognomonic cell-cell fusion (syncytia) associated with many viral infections, such as those of the paramyxoviruses. However, technologies that detect glycoprotein conformational changes on actual enveloped virions are difficult and time-consuming for those viruses for which such detection is possible (1-6). Additionally, there is a great need for rapid identification and characterization of virions in medical, veterinary, or food samples. Having a method with these capabilities would advance the fields of virus diagnosis and analysis.Our model, Nipah virus (NiV), is an enveloped virus in the important Paramyxoviridae family, which comprises human and veterinary enveloped viruses such as measles virus, mumps virus, Newcastle disease virus, respiratory syncytial virus, canine distemper virus, the metapneumoviruses, the human parainfluenza viruses, Hendra virus (HeV), and NiV (6-8). NiV is an emerging zoonotic virus in the Henipavirus genus that causes severe illness in humans, characterized by encephalitis and respiratory disease associated with syncytium formation (7, 9). Although NiV causes 40 to 75% mortality in humans, there is no approved treatment; thus, NiV is classified as a biosafety level 4 agent and a priority pathogen in the NIH/NIAID agenda. Additionally, because paramyxoviruses are relatively stable in aerosols and NiV is capable of animal-to-animal, animal-to-human, and human-to-human transmission, NiV is considered a potential agro-and/or bioterrorism agent (7).Conformational changes of the viral glycoproteins are required for viral entry and cell-cell fusion. However, it is difficult to obtain X-ray crystal structural information from intact full-length glycoproteins because their hydrophobic transmembrane regions are embedded in a lipid membrane. Therefore, structural studies have been skewed toward ectodomain glycoprotein forms because it is relatively more straightforward to obtain structural information for them. Viral glycoprotein conformational changes have typically been observed either by analysis of viral glycoprotein soluble ectodomain forms (e.g., see references 10-12) or by analysis of full-length wild-type glycoproteins expressed on cell surfaces (e.g., see reference 13). Although soluble ectodomains normally bind their respective cell receptors, it is often not possible to assess how accurately their structures and structural changes compare with those of their membrane-bound full-length wild-type counterparts. Moreover, the tendency of soluble glycoprotein ectodomains to adopt postfusion conformations in many cases limits our ability to detect and characterize essential glycoprotein receptorinduced conformational changes (12,14). Analysis of receptorinduced conformational changes of full-length wild-type glycoproteins embedded in cellular or viral membranes is preferred, and even for such analyses, there may be differences in the role...

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Section: Discussionmentioning

confidence: 99%

Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy

Liu

Benavides-Montaño

et al. 2013

J Virol

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“…Traditional vaccines have relied on live-attenuated or inactivated organisms, attenuated bacteria or capsules, or inactivated toxins. 28,29 Progress has been made recently in enhancing immunity through a mechanistic understanding of the biology of dendritic cells and their response to adjuvants. 30 Alternative delivery, including viruslike particles or structured arrays with the use of phage or nanoparticles, also stimulate effective immunity and provide powerful tools to confer protection for a specific pathogen (Fig.…”

Section: Scientific Discovery In the Current Vaccine Eramentioning

confidence: 99%

Designing Tomorrow's Vaccines

2013

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“…A remarkable attribute of prions is their resistance to inactivation by formaldehyde, a fixative that has been used for decades to neutralize viruses in the preparation of vaccines [7]. In the 1930s, W.S.…”

Section: Introductionmentioning

confidence: 99%

Aβ seeds resist inactivation by formaldehyde

Fritschi

Cintron

et al. 2014

Acta Neuropathol

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Cerebral β-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated β-amyloid (Aβ) into young, pre-depositing Aβ precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated Aβ itself. Here we report that the β-amyloid-inducing activity of Alzheimer’s disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated Aβ are maintained in fixed tissues. The resistance of Aβ seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of Aβ aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.

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Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

Cited by 162 publications

References 98 publications

Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy

Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy

Designing Tomorrow's Vaccines

Aβ seeds resist inactivation by formaldehyde

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