Better influenza vaccines: an industry perspective

Chen, Juine-Ruey; Liu, Yo-Min; Tseng, Yeu-Yang; Ma, Che

doi:10.1186/s12929-020-0626-6

Cited by 83 publications

(100 citation statements)

References 88 publications

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“…Vaccination still remains the best protection currently available against seasonal influenza [3]. Among the many types of seasonal influenza vaccines, the most widely used are inactivated influenza vaccines (IIVs) based on influenza virus propagation in chicken embryos [7]. Nevertheless, there are differences in the processes used by manufacturers to obtain the final product, especially at the multistep stage of downstream processing [12].…”

Section: Discussionmentioning

confidence: 99%

“…A relatively small number of vaccines are procured from global manufacturers abroad, i.e., outside the NIP framework. According to the Global Action Plan for Influenza Vaccines (GAP) [6], the global seasonal influenza vaccine production was 1.467 billion doses in 2015, of which 88% were inactivated influenza vaccines (IIVs) produced through influenza virus replication in the allantoic cavity of chicken embryos (i.e., egg-based vaccines) [7].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

et al. 2020

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Background: today’s standard quality control methods used to control the protein composition of inactivated influenza vaccines only take into account a few key reference components. They do not allow for thorough characterization of protein compositions. As a result, observation of unpredictable variations in major viral constituents and admixtures of cellular proteins within manufactured vaccines that may seriously influence the immunogenicity and safety of such vaccines has become a pressing issue in vaccinology. This study aims at testing a more sophisticated approach for analysis of inactivated split influenza vaccines licensed in the Russian Federation. The formulations under study are the most available on the market and are included in the Russian National Immunization Program. Methods: liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, in combination with label-free protein quantitation via the intensity-based absolute-quantitation (iBAQ) algorithm, as well as a number of standard molecular analysis methods, such as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS), and negative-stain transmission electron microscopy (TEM) were applied. Results: the methods implemented were able to identify dozens of viral and host proteins and quantify their relative amounts within the final formulations of different commercially available inactivated split influenza vaccines. Investigation of molecular morphology of the vaccine preparations using TEM revealed typical rosettes of major surface proteins (hemagglutinin and neuraminidase). DLS was used to demonstrate a size distribution of the rosettes and to test the stability of vaccine preparations at increased temperatures. Conclusions: a holistic approach based on modern, highly productive analytical procedures was for the first time applied for a series of different commercially available inactivated split influenza vaccines licensed in Russia. The protocols probed may be suggested for the post-marketing quality control of vaccines. Comparison of different preparations revealed that the Ultrix® and Ultrix® Quadri vaccines produced by pharmaceutical plant FORT LLC and trivalent vaccine Vaxigrip® produced by pharmaceutical company Sanofi Pasteur have well-organized antigen rosettes, they contain fewer admixture quantities of host cell proteins, and demonstrate good correlation among mostly abundant viral proteins detected by different methods.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

et al. 2020

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“…Antigenic drift is the progressive accumulation of point mutations on the influenza virus' surface glycoproteins HA and NA, driven by high error rates of the virus' RNA-dependent RNA polymerase. Moreover, the mutations are positively selected and become fixed, resulting in new strains that differ antigenically from what the host was vaccinated against [134]. The antigenic shift is responsible for the development of the pandemic, and is the reassortment process of gene segments across various strains infecting the same host, resulting in a complete change in antigenicity [122].…”

Section: Influenza Virusesmentioning

confidence: 99%

Dangerous Pathogens as a Potential Problem for Public Health

et al. 2020

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Pathogens are various organisms, such as viruses, bacteria, fungi, and protozoa, which can cause severe illnesses to their hosts. Throughout history, pathogens have accompanied human populations and caused various epidemics. One of the most significant outbreaks was the Black Death, which occurred in the 14th century and caused the death of one-third of Europe’s population. Pathogens have also been studied for their use as biological warfare agents by the former Soviet Union, Japan, and the USA. Among bacteria and viruses, there are high priority agents that have a significant impact on public health. Bacillus anthracis, Francisella tularensis, Yersinia pestis, Variola virus, Filoviruses (Ebola, Marburg), Arenoviruses (Lassa), and influenza viruses are included in this group of agents. Outbreaks and infections caused by them might result in social disruption and panic, which is why special operations are needed for public health preparedness. Antibiotic-resistant bacteria that significantly impede treatment and recovery of patients are also valid threats. Furthermore, recent events related to the massive spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an example of how virus-induced diseases cannot be ignored. The impact of outbreaks, such as SARS-CoV-2, have had far-reaching consequences beyond public health. The economic losses due to lockdowns are difficult to estimate, but it would take years to restore countries to pre-outbreak status. For countries affected by the 2019 coronavirus disease (COVID-19), their health systems have been overwhelmed, resulting in an increase in the mortality rate caused by diseases or injuries. Furthermore, outbreaks, such as SARS-CoV-2, will induce serious, wide-ranging (and possibly long-lasting) psychological problems among, not only health workers, but ordinary citizens (this is due to isolation, quarantine, etc.). The aim of this paper is to present the most dangerous pathogens, as well as general characterizations, mechanisms of action, and treatments.

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“…Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Current seasonal influenza vaccines are effective when vaccine strains are matched with circulating strains [ 2 , 3 ]. However, there is little to no cross-protection against antigenic variants, emerging pandemic or zoonotic outbreak strains [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem

et al. 2020

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Influenza virus infection is a global public health threat. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. There is a critical need for developing “universal” vaccines that protect against all influenza viruses. HA stem is a promising target for developing broad-spectrum influenza vaccines due to its relatively conserved feature. However, HA stem is weakly immunogenic when administered alone in a soluble form. Several approaches have been employed to improve the immunogenicity of HA stem, including conjugation of HA stem with a highly immunogenic carrier protein or displaying HA stem on a nanoparticle scaffold. Converting a weakly immunologic protein into a multimer through aggregation can significantly enhance its immunogenicity, with some multimeric protein aggregates previously shown to be more immunogenic than their soluble counterparts in animal models. Here, we show that a chemically coupling a peptide derived from the head domain of PR8 HA (P35) with the poorly immunogenic HA stem protein results in aggregation of the HA stem which significantly increases stem-specific B cell responses following vaccination. Importantly, vaccination with this conjugate in the absence of adjuvant still induced robust B cell responses against stem in vivo. Improving HA stem immunogenicity by aggregation provides an alternative avenue to conjugation with exotic carrier proteins or nanoparticle formulation.

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Better influenza vaccines: an industry perspective

Cited by 83 publications

References 88 publications

Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

Dangerous Pathogens as a Potential Problem for Public Health

Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem

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