Comparative testing of vaccines based on viruses of genetic lineages G1 and Y280 for their potency against low pathogenic avian influenza H9N2

Due to the genetic diversity of low pathogenic avian influenza (LPAI) viruses of subtype H9N2, it deemed appropriate to study the potency of the vaccines based on the antigens of strains А/chicken/Amursky/03/12 and A/chicken/Chelyabinsk/314-1/20 that represent currently circulating in the Russian Federation genetic lineages Y280 and G1, respectively. While low pathogenicity of the agent does not allow demonstrating the vaccine protective properties by the direct methods generally used for potency assessment (e.g. morbidity and mortality), the indirect methods were used: determination of antigenic relatedness of the strains, level of the postvaccinal homologous and heterologous humoral immunity, analysis of the virus genome synthesis inhibition (reduction) in vaccinated birds following their challenge. The strains used in the vaccines were determined to have some antigenic differences, which were demonstrated in the hemagglutination inhibition (HI) assay during control of the postvaccinal immunity in birds. Both vaccines generally induced strong humoral immunity in vaccinated birds (9–10 log2 determined using HI assay) with some difference in the levels of the immune response following the use of homologous or heterologous antigens. It was also reliably determined that homologous immunity facilitated more expressed inhibition of the virus reproduction after the challenge. The level of inhibition (reduction) of the virulent LPAI virus genome synthesis in vaccinated birds following their challenge with H9N2 virus of genetic lineage G1 was higher in birds following homologous vaccination, while the time periods of the genome detection in the biomaterial samples were the same. It was demonstrated that due to antigenic and immunogenic differences between LPAI H9N2 strains, use of both antigenic components in the inactivated vaccines is appropriate.

Comparative Analysis of Tunisian Sheep-Like Virus, Bungowannah Virus and Border Disease Virus Infection in the Porcine Host

Apart from the established pestivirus species Pestivirus A to Pestivirus K novel species emerged. Pigs represent not only hosts for porcine pestiviruses, but are also susceptible to bovine viral diarrhea virus, border disease virus (BDV) and other ruminant pestiviruses. The present study focused on the characterization of the ovine Tunisian sheep-like virus (TSV) as well as Bungowannah virus (BuPV) and BDV strain Frijters, which were isolated from pigs. For this purpose, we performed genetic characterization based on complete coding sequences, studies on virus replication in cell culture and in domestic pigs, and cross-neutralization assays using experimentally derived sera. TSV forms a distinct phylogenetic group more closely related to Pestivirus C (classical swine fever virus, CSFV) than to Pestivirus D (BDV). In contrast to BDV and BuPV, TSV replicates by far more efficiently on ovine than on porcine cells. Nevertheless, pigs were susceptible to TSV. As a consequence of close antigenic relatedness of TSV to CSFV, cross-reactivity was detected in CSFV-specific antibody assays. In conclusion, TSV is genetically closely related to CSFV and can replicate in domestic pigs. Due to close antigenic relatedness, field infections of pigs with TSV and other ruminant pestiviruses can interfere with serological diagnosis of classical swine fever.

Broadly Reactive IgG Responses to Heterologous H5 Prime-Boost Influenza Vaccination Are Shaped by Antigenic Relatedness to Priming Strains

The antigenic shift and draft of hemagglutinin (HA) in influenza viruses is accepted as one of the major reasons for immune evasion. The analysis of B cell immune responses to influenza infection and vaccination is complicated by the impact of exposure history and antibody cross-reactions between antigenically similar influenza strains.

Broadly-reactive IgG responses to heterologous H5 prime-boost influenza vaccination are shaped by antigenic relatedness to priming strains

Prime-boost vaccinations of humans with different H5 strains have generated broadly protective antibody levels. However, the effect of an individual’s H5 exposure history on antibody responses to subsequent H5 vaccination is poorly understood. To investigate this, we analyzed the IgG response to H5 A/Indonesia/5/2005 (Ind05) vaccination in three cohorts: (1) a double primed group that received two H5 vaccinations: A/Vietnam/203/2004 (Vie04) 5 years ago and A/Hong Kong/156/1997 (HK97) 11 years ago, (2) a single primed group that received Vie04 5 years ago, and (3) an H5-naïve group that received two doses of the Ind05 vaccine 28 days apart. Hemagglutinin (HA)-reactive IgG levels were estimated by multiplex assay against an HA panel that included 21 H5 strains and 9 other strains representing H1, H3, H7, and H9 subtypes. Relative HA antibody landscapes were generated to quantitatively analyze the magnitude and breadth of antibody binding after vaccination. We found that short-interval prime-boosting with the Ind05 in the naïve group generated a low anti-H5 response. Both primed groups generated robust antibody responses reactive to a broad range of H5 strains after boosting with Ind05; IgG antibody levels persisted longer in subjects who had been double primed years ago. Notably, the IgG responses were strongest against the first priming H5 strain, that reflecting influenza virus immune imprinting. Finally, the broad anti-H5 IgG response was stronger against strains having a small antigenic distance to the initial priming strain.

Characterizing genetic and antigenic divergence from vaccine strain of influenza A and B viruses circulating in Thailand, 2017–2020

We monitored the circulating strains and genetic variation among seasonal influenza A and B viruses in Thailand between July 2017 and March 2020. The hemagglutinin gene was amplified and sequenced. We identified amino acid (AA) changes and computed antigenic relatedness using the Pepitope model. Phylogenetic analyses revealed multiple clades/subclades of influenza A(H1N1)pdm09 and A(H3N2) were circulating simultaneously and evolved away from their vaccine strain, but not the influenza B virus. The predominant circulating strains of A(H1N1)pdm09 belonged to 6B.1A1 (2017–2018) and 6B.1A5 (2019–2020) with additional AA substitutions. Clade 3C.2a1b and 3C.2a2 viruses co-circulated in A(H3N2) and clade 3C.3a virus was found in 2020. The B/Victoria-like lineage predominated since 2019 with an additional three AA deletions. Antigenic drift was dominantly facilitated at epitopes Sa and Sb of A(H1N1)pdm09, epitopes A, B, D and E of A(H3N2), and the 120 loop and 190 helix of influenza B virus. Moderate computed antigenic relatedness was observed in A(H1N1)pdm09. The computed antigenic relatedness of A(H3N2) indicated a significant decline in 2019 (9.17%) and 2020 (− 18.94%) whereas the circulating influenza B virus was antigenically similar (94.81%) with its vaccine strain. Our findings offer insights into the genetic divergence from vaccine strains, which could aid vaccine updating.

Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection

Background Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. Results Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. Conclusions Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.

Characterization of Antigenic Relatedness Among GI Norovirus Genotypes Using Serum Samples From Norovirus-Infected Patients and Mouse Sera

Characterizing diversity and the antigenic relatedness of norovirus remains a primary focus in understanding its biological properties and vaccine designs. The precise antigenic and serological features of GI genotypes have not been studied. The study represented an investigation on a gastroenteritis outbreak related to GI.3 norovirus and the three most detected GI genotypes, GI.2 (belonging to immunotype B), GI.3 and GI.9 (belonging to immunotype C), were selected to characterize their phylogenetic relationship, HBGA binding profiles and antigenic relatedness within (intra-immunotype), and between (inter-immunotypes) genotypes using mouse sera and patient’s serum samples from the GI.3 related outbreak. Wide HBGA binding profiles and evolution of binding affinity were observed in the three GI genotypes studied. A low specific blockade antibody to GI.3 in the population generated the pool of susceptible individuals and supported virus spread in the outbreak. We found strong blockade immune response in homologous strains, moderate intra-immunotype blockade but weak inter-immunotypes blockade in humans following GI.3 norovirus infections. These findings further support the immunotypes grouping and will be valuable for optimizing the design of norovirus vaccine.

Molecular and Antigenic Characterization of GI-13 and GI-16 Avian Infectious Bronchitis Virus Isolated in Chile from 2009 to 2017 Regarding 4/91 Vaccine Introduction

The introduction of the 4/91 vaccine against infectious bronchitis in Chile, a lineage not described until that time in the country, led to looking for changes induced by this action. This study considers eight isolates obtained from 2009, 2015 and 2017 and uses a maximum likelihood approach to classify the field isolates. Three isolates were selected to analyze antigenic relationships through a virus neutralization test and to perform protection tests measured trough an RT-qPCR. The isolates from 2009 and 2015 showed a relationship with GI-16 while those from 2017 were related to GI-13. Though the field isolates were classified in two different phylogenetic lineages, all of them showed only minor variations in subtype. The 13885R-17 isolate from 2017 exhibited high antigenic relatedness to the 4/91 vaccine. As expected, 4/91 and Massachusetts vaccines were not antigenically related. Vaccinated birds with the 4/91 vaccine showed less tracheal virus replication for the 13885R-17 from 2017 challenge than for the 12101SP-09 from 2009 and 13347SP-15 from 2015 isolates. The results indicated genetic and antigenic diversity in the most recent infectious bronchitis virus (IBV) isolates in Chile. Moreover, the 4/91 vaccine would be involved in the generation of some current field viruses, which must be considered in vaccination programs and public policies.