Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these vaccines have faults, such as ...reactivity or suboptimal efficacy and expensive and time-consuming development and production. Additionally, despite the enormous efforts to develop vaccines against some infectious diseases, the traditional technologies have not been successful in achieving this. At the same time, the concerns about emerging and re-emerging diseases urge the need to develop technologies that can be rapidly applied to combat the new challenges. Within the last two decades, the research of vaccine technologies has taken several directions to achieve safe, efficient, and economic platforms or technologies for novel vaccines. This review will give a brief overview of the current state of the novel vaccine technologies, new vaccine candidates in clinical trial phases 1–3 (listed by European Medicines Agency (EMA) and Food and Drug Administration (FDA)), and vaccines based on the novel technologies which have already been commercially available (approved by EMA and FDA) with the special reference to pandemic COVID-19 vaccines.
Key points
• Vaccines of the new generation follow the minimalist strategy.
• Some infectious diseases remain a challenge for the vaccine development.
• The number of new vaccine candidates in the late phase clinical trials remains low.
Negative-stranded RNA viruses (NSVs) are important human pathogens, including emerging and reemerging viruses that cause respiratory, hemorrhagic and other severe illnesses. Vaccine design ...traditionally relies on the viral surface glycoproteins. However, surface glycoproteins rarely elicit effective long-term immunity due to high variability. Therefore, an alternative approach is to include conserved structural proteins such as nucleoprotein (NP). NP is engaged in myriad processes in the viral life cycle: coating and protection of viral RNA, regulation of transcription/replication processes and induction of immunosuppression of the host. A broad heterosubtypic T-cellular protection was ascribed very early to this protein. In contrast, the understanding of the humoral immunity to NP is very limited in spite of the high titer of non-neutralizing NP-specific antibodies raised upon natural infection or immunization. In this review, the data with important implications for the understanding of the role of NP in the immune response to human NSVs are revisited. Major implications of the elicited T-cell immune responses to NP are evaluated, and the possible multiple mechanisms of the neglected humoral response to NP are discussed. The intention of this review is to remind that NP is a very promising target for the development of future vaccines.
In spite of the success of the mumps vaccination, recent mumps outbreaks have been reported even among individuals with a history of mumps vaccination. For a better understanding of why the ...vaccination failed in cases of vaccinees who fell ill during recent mumps outbreaks, the immunological events during infection and/or vaccination should be better defined. In the work presented here we sought to identify new neutralization sites on the mumps virus surface glycoproteins. By using anti-mumps mAbs, three amino acid positions at residues 221, 323 and 373 in the F protein of mumps virus were shown to be located in at least two conformational neutralization epitopes. mAbs that specifically target these sites effectively neutralized mumps virus in vitro. The newly acquired glycosylation site at position 373 or loss of the existing one at position 323 was identified as the mechanism behind the escape from the specific mAbs. Based on the findings of this study, we suggest that the influence of the antigenic structure of the F protein should not be ignored in a thorough investigation of the underlying mechanism of the mumps vaccine failure or when making a strategy for development of a new vaccine.
Immunization programs have implemented live attenuated mumps vaccines which reduced mumps incidence ≥97%. Some of the vaccine strains were abandoned due to unwanted side effects and the genetic ...marker of attenuation has not been identified so far. Our hypothesis was that non-infectious viral particles, in particular defective interfering particles (DIPs), contribute to neuroattenuation. We showed that non-infectious particles of the mumps vaccine L-Zagreb attenuated neurovirulence of wild type mumps virus 9218/Zg98. Then, we attenuated recent wild type mumps virus MuVi/Zagreb.HRV/28.12 in Vero cells through 16 passages but already the fifth passage (p5) showed accumulation of DIPs and attenuated neurovirulence in a newborn rat model when compared to the second passage (p2). Sequence analysis of the p2 and p5 revealed a single mutation in the 5′ untranslated region of the HN gene. Analysis of the expression level of the HN protein showed that this mutation does not affect the expression of the protein. We conclude that the passages of MuVi/Zagreb.HRV/28.12 in Vero cells for only three passages accumulated DIPs which attenuate neurovirulence.
These findings reveal DIPs as a very promising and general neuroattenuating factor which should be considered in the rational design of the new mumps vaccine.
Comparative genomics of human rubulavirus 2 Šantak, Maja; Mlinarić-Galinović, Gordana; Vilibić-Čavlek, Tatjana ...
Archives of virology,
11/2018, Volume:
163, Issue:
11
Journal Article
Peer reviewed
Although human rubulavirus 2 (HPIV2) is an important respiratory pathogen, little is known about its molecular epidemiology. We performed a comparative analysis of the full-length genomes of fourteen ...HPIV2 isolates belonging to different genotypes. Additionally, evolutionary analyses (phylogenetic reconstruction, sequence identity, detection of recombination and adaptive evolution) were conducted. Our study presents a systematic comparative genetic analysis that complements prior analyses and utilizes full-length HPIV2 genomes to provide a basis for future work on the clinical significance, molecular variation and conservation, and evolution of HPIV2.
Influenza viruses have been with mankind for at least 300 years, with
epidemics occurring every few years and pandemics every few decades. They replicate extremely rapidly in the host therefore ...demanding a fast and
effective antiviral response. Despite the availability of seasonal trivalent
vaccines and antivirals, which are effective for most recipients, influenza
remains serious disease. The reason for that is a grand capacity of the
influenza virus to adapt to new environmental conditions and evolutionary
pressure. Vaccination remains the main protective measure against influenza for general population. The first vaccine was administered in the 1940s and ever since the influenza vaccine has provided tremendous relief against influenza infections. However, time has revealed the ultimate limit of the vaccine and the call for its reinvention has now come. The purpose of this review is to give a brief but comprehensive overview of the currently used prophylactic and therapeutic approaches against influenza and the new most promising developments in this field.
Background Commercial preparations of native human interferon alpha (nHuIFN-α) contain several subtypes of interferon-alpha (IFN-α) and traces of other cytokines. Recently, we described its ...antifibrotic potential and showed nHuIFN-α to have a greater effect than that of recombinant human IFN-α (rHuIFN-α). We hypothesized that cooperation between different cytokines in the nHuIFN-α preparation is essential for this effect. Considerable concentrations of interleukin-1β (IL-1β) and platelet-derived growth factor AB (PDGF-AB) are present in the nHuIFN-α preparations. Methods We tested the viability and the expression of procollagen type I messenger RNA (mRNA) in MRC5 fibroblasts treated with interleukin-1 beta (IL-1β) and/or PDGF-AB, or the corresponding antibodies in combination with rHuIFN-α or nHuIFN-α. Results We showed that neither IL-1β nor PDGF-AB significantly affect the viability of MRC5 cells. Furthermore, cell viability was not affected when IL-1β or PDGF-AB were applied along with rHuIFN-α, relative to the viability of cells treated with rHuIFN-α only. In contrast, both cytokines suppressed the synthesis of procollagen type I mRNA. When coadministered with rHuIFN-α, IL-1β enhanced the suppression induced by rHuIFN-α. Conversely, PDGF-AB acted as an antagonist of rHuIFN-α and restored partially the synthesis of procollagen type I mRNA. Interestingly, the addition of IL-1β to the PDGF-AB/rHuIFN-α mix not only abolished the antagonistic activity of PDGF-AB but also decreased the synthesis of procollagen type I mRNA beyond the level achieved by IL-1β/rHuIFN-α. Therefore, IL-1β was able to reverse the activity of PDGF-AB. Conclusion Our study suggests that IL-1β is an important component of nHuIFN-α preparations, acting directly and indirectly to modulate the action of other components. This study provides insight into these complex cytokine networks, which is necessary for better and safer antifibrotic therapy.
Abstract The two most commonly used methods for the determination of a virus potency are plaque assay and 50% cell culture infective dose (CCID50 ) assay, both based on cytopathic effect observation. ...We compared the potency estimates obtained by plaque and CCID50 assays for nine mumps virus strains that produce different cytopathic effects in Vero cells. The ratios of CCID50 and plaque assay quantification results differed for different strains and were in a range of 0.66–10, indicating that quantification results for some mumps virus strains are almost identical regardless of whether CCID50 or plaque method is used, while the potency estimates of other strains strongly depend on the choice of the assay.
The canonical genome organization of measles virus (MV) is characterized by total size of 15 894 nucleotides (nts) and defined length of every genomic region, both coding and non-coding. Only rarely ...have reports of strains possessing non-canonical genomic properties (possessing indels, with or without the change of total genome length) been published. The observed mutations are mutually compensatory in a sense that the total genome length remains polyhexameric. Although programmed and highly precise pseudo-templated nucleotide additions during transcription are inherent to polymerases of all viruses belonging to family Paramyxoviridae, a similar mechanism that would serve to non-randomly correct genome length, if an indel has occurred during replication, has so far not been described in the context of a complete virus genome.
We compiled all complete MV genomic sequences (64 in total) available in open access sequence databases. Multiple sequence comparisons and phylogenetic analyses were performed with the aim of exploring whether non-recombinant and non-evolutionary linked measles strains that show deviations from canonical genome organization possess a common genetic characteristic.
In 11 MV sequences we detected deviations from canonical genome organization due to short indels located within homopolymeric stretches or next to them. In nine out of 11 identified non-canonical MV sequences, a common feature was observed: one mutation, either an insertion or a deletion, was located in a 28 nts long region in F gene 5' untranslated region (positions 5051-5078 in genomic cDNA of canonical strains). This segment is composed of five tandemly linked homopolymeric stretches, its consensus sequence is G6-7C7-8A6-7G1-3C5-6. Although none of the mononucleotide repeats within this segment has fixed length, the total number of nts in canonical strains is always 28. These nine non-canonical strains, as well as the tenth (not mutated in 5051-5078 segment), can be grouped in three clusters, based on their passage histories/epidemiological data/genetic similarities. There are no indications that the 3 clusters are evolutionary linked, other than the fact that they all belong to clade D.
A common narrow genomic region was found to be mutated in different, non-related, wild type strains suggesting that this region might have a function in non-random genome length corrections occurring during MV replication.
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