A bioinformatics approach for identifying the probable cause of the cross-interaction of antibodies to the antigenic protein HPV16 L1 with the HPV6 L1 protein

This paper describes an attempt to analyze, with the aid of bioinformatics resources (programs and databases), the probable cause of the cross-interaction of antibodies against HPV16 L1 with antigenic protein HPV6 L1, which has been revealed in the investigation of the candidate vaccine obtained on the base of a plant expression system (tomato plants). In our opinion, the most likely reason for the cross-interaction of antibodies with antigens of different pathogenic HPV types is the similarity of their antigenic determinants. In this work, the amino acid sequences of HPV16 L1 and HPV6 L1 used for the development of a binary vaccine against cervical cancer and anogenital papillomatosis have been analyzed. For the analysis of antigenic determinants, the programs BepiPred-2.0: Sequential B-Cell Epitope Predictor, DiscoTope 2.0 Server and SYFPEITHI have been used. As a result of the analysis of probable B-cell linear determinants (epitopes), it has been found that in both types of HPV the proteins have approximately the same location and size of linear antigenic determinants; the difference is observed only in the form of small shifts in the size of several amino acid residues. However, there are some differences in the amino acid composition of epitopes; therefore, the possibility for cross-interaction of the antibodies with the antigens due to the similarity of linear antigenic determinants for B-cells is very small. The analysis of potential threedimensional epitopes for B-cells has shown that due to little difference between them the HPV16 L1 and HPV6 L1 proteins have no prerequisites for cross-interaction of the antibodies with the antigens belonging to the two different pathogenic HPV types. The analysis of probable linear epitopes for T-cells has revealed a common antigenic determinant in the two protein sequences. According to the rank made with the SYFPEITHI program, the amino acid sequence AQL(I)FNKPYWL is the second most likely antigenic determinant for T-cells. Meanwhile, the amino acid sequences of this determinant in HPV16 L1 and HPV6 L1 are virtually identical. There is a difference in only one position, but it is not critical due to the similarity of the physicochemical properties of amino acids, for which there is a replacement in the amino acid sequence of antigenic determinants. Consequently, some moderate cross-interaction of the antibodies to HPV16 L1 with the antigens of HPV6 L1 may be expected.

Physical properties as antigenic determinant: the example of antiphospholipid antibodies

Although the specificity of an antibody grows through process requiring somatic mutation, the Ag-binding polyspecificity of an antibody enlarges the Ag detection of the immune system. While the polyspecificity of antibody is its ability to bind at least two different Ags, apparent polyspecificity could also depends of characteristics of Ag considered. Whichever the type of epitopes, conformational or linear, they are commonly determined by the surface of the involved epitope residues. We demonstrate that the apparent polyspecificity of antiphospholipid antibody responsible for the antiphospholipid syndrome is due to an epitope characterized by the physical properties of amino acids whose polarity, hydropathy and steric volume but not by the sequence of residues. The physicals properties are, per se, the epitope for certain antibody. Although this novel concept provides insights on how the polyspecificity of an antibody can be linked up under the lead of a common motif of physical properties.

Spike S2 Subunit: The Dark Horse in the Race for Prophylactic and Therapeutic Interventions against SARS-CoV-2

In the midst of the unceasing COVID-19 pandemic, the identification of immunogenic epitopes in the SARS-CoV-2 spike (S) glycoprotein plays a vital role in the advancement and development of intervention strategies. S is expressed on the exterior of the SARS-CoV-2 virion and contains two subunits, namely the N-terminal S1 and C-terminal S2. It is the key element for mediating viral entry as well as a crucial antigenic determinant capable of stimulating protective immune response through elicitation of anti-SARS-CoV-2 antibodies and activation of CD4+ and CD8+ cells in COVID-19 patients. Given that S2 is highly conserved in comparison to the S1, here, we provide a review of the latest findings on the SARS-CoV-2 S2 subunit and further discuss its potential as an attractive and promising target for the development of prophylactic vaccines and therapeutic agents against COVID-19.

A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis

An increased incidence of narcolepsy type 1 (NT1) was observed in Scandinavia following the 2009–2010 influenza Pandemrix vaccination. The association between NT1 and HLA-DQB1*06:02:01 supported the view of the vaccine as an etiological agent. A/H1N1 hemagglutinin (HA) is the main antigenic determinant of the host neutralization antibody response. Using two different immunoassays, the Luciferase Immunoprecipitation System (LIPS) and Radiobinding Assay (RBA), we investigated HA antibody levels and affinity in an exploratory and in a confirmatory cohort of Swedish NT1 patients and healthy controls vaccinated with Pandemrix. HA antibodies were increased in NT1 patients compared to controls in the exploratory (LIPS p = 0.0295, RBA p = 0.0369) but not in the confirmatory cohort (LIPS p = 0.55, RBA p = 0.625). HA antibody affinity, assessed by competition with Pandemrix vaccine, was comparable between patients and controls (LIPS: 48 vs. 39 ng/ml, p = 0.81; RBA: 472 vs. 491 ng/ml, p = 0.65). The LIPS assay also detected higher HA antibody titres as associated with HLA-DQB1*06:02:01 (p = 0.02). Our study shows that following Pandemrix vaccination, HA antibodies levels and affinity were comparable NT1 patients and controls and suggests that HA antibodies are unlikely to play a role in NT1 pathogenesis.

Molecular Epidemiology of Bordetella pertussis Strains Isolated in Vietnam During 2015–2017

Background: Whooping cough is a serious respiratory illness in infants caused by Bordetella pertussis. In spite of the vaccination program, the incidence rates of whooping cough per 100,000 population in Vietnam increased from 0.33 in 2015 to 0.58 in 2017. If this represents a pertussis resurgence, contributors may include pathogen adaptation, the spread of specific variants, vaccine failure, and failure to effectively treat cases and contacts. There has been little research in Vietnam on B. pertussis strains. Therefore, we investigated the molecular epidemiology of circulating B. pertussis strains in Southern Vietnam by applying multilocus sequence typing (MLST) for 7 housekeeping genes and 4 antigenic determinant genes as components in the acellular vaccine including prn, ptxP, ptxS1, and fim3. Methods: DNA was extracted from 15 isolates collected from 263 case patients during 2015–2017 and was subject to MLST using primers and cycling conditions from the Bordetella pubMLST website (www.Pubmlst.org/Bordetella/). The products were analyzed using BioEdit version 7.2.5 software and then were aligned and compared to reference sequences of each genotype in the database. The evolutionary relationship among sequence types (STs) from housekeeping genes was performed as a minimum spanning tree via the goeBURST algorithm, whereas the correlation of different variants from 4 antigenic determinant genes was built up and clarified with phylogenetic trees based on the UPGMA method by MEGA 7 program. Results: The 15 isolates were all classified as ST2 (100%) by MLST of housekeeping genes, and they belonged to a common global clonal group (Fig. 1). Sequencing of antigenic determinant genes prn2 – ptxP3 – ptxS1-1 – fim3-1 determined that all were identical to each another and the reference sequences (Fig. 2). Conclusions:B. pertussis isolates circulating in Southern Vietnam appeared to be the same as the common global strain. Few isolates were available for testing; therefore, continued surveillance is important to confirm these findings and to monitor population changes over time.Funding: NoneDisclosures: None

Metapneumovirus humano: epidemiología y posibles tratamientos profilácticos

In 2001 in the Netherlands, Human metapneumovirus (hMPV) was identified as a “new” etiologic agent causing acute respiratory infections in children younger than 5 years old; however, it has also been isolated in the elderly and immunocompromised people. This virus is considered the second etiological agent in acute diseases of the respiratory tract. Currently, the estimated cost of IRAs in our country is of 9,000USD per inpatient. hMPV is a member of the genus Metapneumovirus, family Pneumoviridae, and it belongs to the order Mononegavirales that is part of the negative single-stranded ribonucleic acid (RNA) virus, consisting of eight genes ordered: 3’-N-P-M-FM2-SH-G-L-5 ‘, and which encodes for 9 proteins. Of these proteins, the F fusion glycoprotein is highly conserved in the genus Metapneumovirus, and is the major antigenic determinant, and because an approved vaccine doesn’t exist, it has been used as a candidate epitope for the design of a vaccine that confers host immunity or as a therapeutic target in the creation of antiviral peptides that inhibit the fusion of the virus to its target cell and to avoid infection in subjects at high risk of contagion since there is currently none accepted by COFEPRIS as a prophylactic treatment against hMPV. Key words: hMPV; respiratory infections; epitopes; protein F;vaccines.

The Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) gH/gL Complex Is the Predominant Neutralizing Antigenic Determinant in KSHV-Infected Individuals

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that plasma from a majority of KSHV neutralizers recognizes multiple viral glycoproteins. Moreover, the breadth of nAbs responses against these viral glycoproteins varies among endemic KS, epidemic KS and asymptomatic KSHV-infected individuals. Importantly, among the KSHV glycoproteins, the gH/gL complex, but neither gH nor gL alone, showed the highest adsorption of KSHV-specific nAbs. This activity was detected in 80% of the KSHV-infected individuals regardless of their KS status. The findings suggest that the gH/gL complex is the predominant antigenic determinant of KSHV-specific nAbs. Therefore, gH/gL is a potential target for development of KSHV prophylactic vaccines.