Publications

The Pirbright Institute publication directory contains details of selected publications written by our researchers.

There were a total of 2299 results for your search.

Abstract

The recent emergence and circulation of the A/ASIA/G-VII (A/G-VII) lineage of foot-and-mouth disease virus (FMDV) in the Middle East has resulted in the development of homologous vaccines to ensure susceptible animals are sufficiently protected against clinical disease. However, a second serotype A lineage called A/ASIA/Iran-05 (A/IRN/05) continues to circulate in the region and it is therefore imperative to ensure vaccine strains used will protect against both lineages. In addition, for FMDV vaccine banks that usually hold a limited number of strains, it is necessary to include strains with a broad antigenic coverage. To assess the cross protective ability of an A/G-VII emergency vaccine (formulated at 43 (95% CI 8–230) PD50/dose as determined during homologous challenge), we performed a heterologous potency test according to the European Pharmacopoeia design using a field isolate from the A/IRN/05 lineage as the challenge virus. The estimated heterologous potency in this study was 2.0 (95% CI 0.4–6.0) PD50/dose, which is below the minimum potency recommended by the World Organisation for Animal Health (OIE). Furthermore, the cross-reactive antibody titres against the heterologous challenge virus were poor (≤log10 0.9), even in those cattle that had received the full dose of vaccine. The geometric mean r1-value was 0.2 (95% CI 0.03–0.8), similar to the potency ratio of 0.04 (95% CI 0.004–0.3). Vaccination decreased viraemia and virus excretion compared to the unvaccinated controls. Our results indicate that this A/G-VII vaccine does not provide sufficient protection against viruses belonging to the A/IRN/05 lineage and therefore the A/G-VII vaccine strain cannot replace the A/IRN/05 vaccine strain but could be considered an additional strain for use in vaccines and antigen banks.

Abstract

Background

African swine fever (ASF) is a highly contagious and deadly viral disease affecting domestic and wild pigs of all ages. African swine fever virus (ASFV) has spread rapidly through Eastern and Southeastern Asia first appearing in Vietnam in 2019.

Objectives

Molecular typing of African swine fever virus (ASFV) in Vietnam has identified two principal variants circulating based on the sequencing of the intergenic region (IRG) between the I73R and I329L genes. Identification of additional genetic markers would enable higher resolution tracing of outbreaks within the country.

Methods

Sequence analysis suggested the IRG between the A179L and A137R genes may also exhibit variability, PCR primers were designed and samples from Vietnam were subject to Sanger sequencing.

Results

We developed a novel method for sub-grouping of ASFV based on the IRG between the A179L and A137R genes of ASFV. Our results demonstrated that the finding of the insertion or deletion of an 11- nucleotide sequence (GATACAATTGT) between the A179L-A137R genes.

Conclusions

The sub-grouping method may provide useful insights into the evolution of genotype II ASFV as well as providing evidence of a relationship between geographically separated outbreaks.

Abstract

At the end of 2021 a new SARS-CoV-2 variant, Omicron, emerged and quickly spread across the world. It has been demonstrated that Omicron’s high number of Spike mutations lead to partial immune evasion from even polyclonal antibody responses, allowing frequent re-infection and vaccine breakthroughs. However, it seems unlikely these antigenic differences alone explain its rapid growth; here we show Omicron replicates rapidly in human primary airway cultures, more so even than the previously dominant variant of concern, Delta. Omicron Spike continues to use human ACE2 as its primary receptor, to which it binds more strongly than other variants. Omicron Spike mediates enhanced entry into cells expressing several different animal ACE2s, including various domestic avian species, horseshoe bats and mice suggesting it has an increased propensity for reverse zoonosis and is more likely than previous variants to establish an animal reservoir of SARS-CoV-2. Unlike other SARS-CoV-2 variants, however, Omicron Spike has a diminished ability to induce syncytia formation. Furthermore, Omicron is capable of efficiently entering cells in a TMPRSS2-independent manner, via the endosomal route. We posit this enables Omicron to infect a greater number of cells in the respiratory epithelium, allowing it to be more infectious at lower exposure doses, and resulting in enhanced intrinsic transmissibility.

Abstract

The success of public health interventions is highly dependent on the compliance of the general population. State authorities often implement policies without consulting representatives of faith-based communities, thereby overlooking potential implications of public health measures for these parts of society. Although ubiquitous, these challenges are more readily observable in highly religious states. Romania serves as an illustrative example for this, as recent data identify it as the most religious country in Europe. In this paper, we discuss the contributions of the Romanian Orthodox Church (ROC), the major religious institution in the country, to the national COVID-19 mitigation efforts. We present not only the positive outcomes of productive consultations between public health authorities and religious institutions but also the detrimental impact of unidirectional communication. Our work highlights that an efficient dialogue with faith-based communities can greatly enhance the results of public health interventions. As the outlined principles apply to a variety of contexts, the lessons learned from this case study can be generalized into a set of policy recommendations for the betterment of future public health initiatives worldwide.

Dascalu S, Geambasu O, Valentin Raiu C, Azoicai D, Damian Popovici E, Apetrei C (2021)

COVID-19 in Romania: what went wrong?

Frontiers in Public Health 9, 813941

Abstract

A catastrophic fourth wave of the COVID-19 pandemic in Romania raised international concern due to a rapid surge in the number of infections and the high associated mortality. 

Siddiqui H A, Harvey-Samuel T, Mansoor S (2021)

Gene drive: a faster route to plant improvement

Trends in Plant Science 26 (12), 1204-1206

Abstract

Gene drives for control of vector-borne diseases have been demonstrated in insects but remain challenging in plants. Theoretically, they could be transformative in speeding breeding programs and contributing to food security through providing novel weed control methods. Zhang et al. now report the possibility of implementing gene drive in plants for the first time.

Clements A L, Peacock T P, Sealy J E, Lee H M, Hussain S, Sadeyen J-R, Shelton H, Digard P, Iqbal M (2021)

PA-X is an avian virulence factor in H9N2 avian influenza virus

Journal of General Virology 102 (3), 1531

Abstract

Influenza A viruses encode several accessory proteins that have host- and strainspecific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focussing on the natural avian host, chickens. We found that the G1 lineage A/chicken/Pakistan/UDL-01/2008 (H9N2) PA-X induced robust host shutoff in both mammalian and avian cells and increased virus replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethality in ovo and led to more rapid viral shedding and widespread organ dissemination in vivo in chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.

Abstract

Glycans on envelope glycoprotein (Env) of the subgroup J avian leukosis virus (ALV-J) play an essential role in virion integrity and infection process. In this study, we found that among the 13 predicted N-linked glycosylation sites (NGSs) in gp85 of Tibetan chicken strain TBC-J6, N17 and N193/N191 are pivotal in the virus replication. Further research illustrated that mutation at N193 weakened Env-receptor binding in blocking assay of viral entrance, co-immunoprecipitation and ELISA. Our studies also showed that N17 was involved in Env protein processing and later virion incorporation, based on the detection of p27 and Env protein in the supernatant and gp37 in the cell culture. This report is a systematic research on clarifying the biological function of NGSs on ALV-J gp85, which would provide valuable insights in the role of gp85 in ALV life cycle as well as anti-ALV-J strategies. Importance ALV-J is a retrovirus that can cause multiple types of tumors in chickens. Among all the viral proteins, the heavily glycosylated envelope protein is especially crucial. Glycosylation plays a major role in Env protein function, including protein processing, receptor attachment and immune evasion. Notably, viruses isolated recently seem to lose the 6(th) and 11(st) NGSs, which are proved to be important in receptor binding. In our study, the 1(st) (N17) and 8(th) (N193) NGS of gp85 of strain TBC-J6 can largely influence the titer of this virus. Deglycosylation at N193 weakened Env-receptor binding, while mutation at N17 influenced Env protein processing. This study systemically analyzed the function of NGSs in ALV-J in different aspects, which may help us to understand the lifecycle of ALV-J and provide antiviral targets for the control of ALV-J.

Abstract

We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160-163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed.

Newman J, Thakur N, Peacock T P, Bialy D, Elreafey A M E, Bogaardt C, Horton D L, Ho S, Kankeyan T, Carr C, Hoschler K, Barclay W S, Amirthalingam G, Brown K, Charleston B, Bailey D (2021)

Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2

medRxiv

Abstract

SARS-CoV-2 variants threaten the effectiveness of tools we have developed to mitigate against serious COVID-19. This is especially true in clinically vulnerable sections of society including the elderly. Using sera from BNT162b2 (Pfizer–BioNTech) vaccinated individuals aged between 70 and 89 (vaccinated with two doses 3-weeks apart) we examined the neutralising antibody (nAb) response to wildtype SARS-CoV-2. Between 3 and 20-weeks post 2nd dose, nAb titres dropped 4.9-fold to a median titre of 21.3 (ND80) with 21.6% of individuals having no detectable nAbs at the later time point. Experiments examining the neutralisation of twenty-one different SARS-CoV-2 variant spike proteins confirmed a significant potential for antigenic escape, especially for the Omicron (BA.1), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 variants. Interestingly, however, the recently-emerged sub-lineage AY.4.2 was more efficiently neutralised than parental Delta pseudotypes. Combining pseudotype neutralisation with specific receptor binding domain (RBD) ELISAs we confirmed that changes to position 484 in the spike RBD were predominantly responsible for SARS-CoV-2 nAb escape, although the effect of spike mutations is both combinatorial and additive. Lastly, using sera from the same individuals boosted with a 3rd dose of BNT162b2 we showed that high overall levels of neutralising antibody titre can provide significant levels of cross-protection against Omicron. These data provide evidence that SARS-CoV-2 neutralising antibodies wane over time and that antigenically variable SARS-CoV-2 variants are circulating, highlighting the importance of ongoing surveillance and booster programmes. Furthermore, they provide important data to inform risk assessment of new SARS-CoV-2 variants, such as Omicron, as they emerge.

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