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Enterovirus-Specific Anti-peptide Antibodies

Poh CL, Kirk K, Chua HN, Grollo L

Methods Mol Biol, 2015;1348:341-50.
PMID: 26424285 DOI: 10.1007/978-1-4939-2999-3_29

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.

Matched MeSH terms: Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte
Expression and Purification of E2 Glycoprotein from Insect Cells (Sf9) for Use in Serology

Chua CL, Sam IC, Chan YF

Methods Mol Biol, 2016;1426:51-61.
PMID: 27233260 DOI: 10.1007/978-1-4939-3618-2_5

Chikungunya virus (CHIKV) is a mosquito-borne arbovirus which poses a major threat to global public health. Definitive CHIKV diagnosis is crucial, especially in distinguishing the disease from dengue virus, which co-circulates in endemic areas and shares the same mosquito vectors. Laboratory diagnosis is mainly based on serological or molecular approaches. The E2 glycoprotein is a good candidate for serological diagnosis since it is the immunodominant antigen during the course of infection, and reacts with seropositive CHIKV sera. In this chapter, we describe the generation of stable clone Sf9 (Spodoptera frugiperda) cells expressing secreted, soluble, and native recombinant CHIKV E2 glycoprotein. We use direct plasmid expression in insect cells, rather than the traditional technique of generating recombinant baculovirus. This recombinant protein is useful for serological diagnosis of CHIKV infection.

Matched MeSH terms: Immunodominant Epitopes/immunology
Fulltext Antibodies to somatic L3 antigen not protective against Brugia malayi infection

Noordin R, Abdullah KA, Azahri NA, Ramachandran CP

Southeast Asian J. Trop. Med. Public Health, 1999 Dec;30(4):678-81.
PMID: 10928359

Western blot analysis of infective larvae (L3) antigen of Brugia malayi were performed on 200 sera from six groups of individuals: 36 samples from B. malayi microfilaremic individuals; 10 samples from individuals with elephantiasis; 50 and 20 samples from amicrofilaremic individuals in a B. malayi endemic area with no anti-filarial IgG4 antibodies (towards microfilaria and adult worm antigens) and samples with high titres of the anti-filarial IgG4 antibodies respectively; 50 samples from non-endemic normals and 34 samples from geohelminth-infected individuals. After protein transfer, PVDF membrane strips were successively incubated with blocking solution, human sera, monoclonal anti-human IgG4 antibody-HRP and developed with luminol chemiluminescence substrate. 28/36 (78%), 1/10 (10%) and 16/20(80%) of sera from individuals with microfilariae, elephantiasis and amicrofilaremic individuals with high titers of anti-filarial IgG4 antibodies respectively recognized L3 antigenic epitopes; the dominant and consistent antigenic bands were of approximately MW 43 kDa, 14 kDa, 15 kDa and 59 kDa. The rest of the sera were unreactive. This study showed that microfilaremics may or may not mount a notable antibody response to somatic L3 antigens, thus lending evidence that antibody response to this antigen is not protective against establishment of Brugia malayi infection.

Matched MeSH terms: Epitopes/immunology
Fulltext Antibody responses of dengue fever patients to dengue 2 (New Guinea C strain) viral proteins

AbuBakar S, Azmi A, Mohamed-Saad N, Shafee N, Chee HY

Malays J Pathol, 1997 Jun;19(1):41-51.
PMID: 10879241

The present study was undertaken to investigate the antibody responses of dengue fever (DF) patients to specific dengue virus proteins. Partially purified dengue 2 New Guinea C (NGC) strain virus was used as antigen. Under the present experimental protocols, it was observed that almost all DF patients' sera had detectable presence of antibodies which recognize the dengue 2 envelope (E) protein. The convalescent-phase sera especially had significant detectable IgG, IgM and IgE against the protein. In addition, IgGs specific against the NS1 dimer and PrM were also detected. Antibody against the core (C) protein, however, was not detectable in any of the DF patients' sera. The substantial presence of IgG against the PrM in the convalescent-phase sera, and the presence of IgE specific for the E, reflect the potential importance of these antibody responses in the pathogenesis of dengue.

Matched MeSH terms: Epitopes/immunology
Conserved and variant epitopes of target antigens of transmission-blocking antibodies among isolates of Plasmodium falciparum from Malaysia

Foo A, Carter R, Lambros C, Graves P, Quakyi I, Targett GA, et al.

Am J Trop Med Hyg, 1991 Jun;44(6):623-31.
PMID: 1713424

Monoclonal antibodies (MAbs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of Plasmodium falciparum, Pfs 25, Pfs 230, and Pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of P. falciparum from Malaysia, using immunofluorescence microscopy (IFA). Among 45 Malaysian isolates, one epitope of Pfs 25, designated region I, showed evidence of variable reactivity with MAbs among different isolates; the Pfs 25 epitope, region II, was universally recognized by MAbs in all isolates. Two apparently distinct epitope regions of Pfs 230 were defined by MAbs, one of which was universally recognized by MAbs among the 45 isolates; the other was conserved in all but three isolates. The epitope regions of gamete-surface protein Pfs 48/45, designated regions I, IIa, IIb, IIc, III, and IV, were examined for reactivity by IFA in 33 isolates. Epitope regions I, IIb, III, and IV were conserved in all isolates; regions IIa and IIc existed in variant forms.

Matched MeSH terms: Epitopes/immunology
Hepatitis B surface antigen subtypes in Malaysia

Kamath S

Am J Epidemiol, 1975 Aug;102(2):191-5.
PMID: 50735

One hundred and ninety hepatitis B surface antigen positive (HBsAG+) sera were subtyped, belonging to : blood donors, hepatitis patients, patients and staff in a hemodialysis unit, all from Kuala Lumpur; Malaysian aborigines from three jungle locations in Peninsular Malaysia; and East Malaysians from Sarawak, East Malaysia; Three subtypes adr, adw and ayw were present in Malaysia in the following frequencies: 44%, 29%, and 27%, respectively; In Kuala Lumpur 87% had subdeterminant d and 13 per cent y, whereas in the deep jungle aborigines of Perak and Pahang, the y subdeterminant was present in 87% and the d in 13%. A similar pattern of preponderance of y prevailed in Sarawak, East Malaysia. In Kuala Lumpur the two main ethnic groups, Malays and Chinese, differed in subtype distribution, in that adr predominated in the Malays (61%), while the adw predominated in the Chinese (51%); Subtype distribution was not related to age or sex of carriers of the antigen, or to whether they had hepatitis, or asymptomatic antigenemia.

Matched MeSH terms: Epitopes*
Fulltext Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design

Chong LC, Khan AM

BMC Genomics, 2019 Dec 24;20(Suppl 9):921.
PMID: 31874646 DOI: 10.1186/s12864-019-6311-z

BACKGROUND: The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome.
METHODS: All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database.
RESULTS: A total of 2321 nonamers met the HCSS selection criteria of entropy 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity.
CONCLUSION: This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.

Matched MeSH terms: Epitopes, T-Lymphocyte/chemistry
Prediction of promiscuous epitopes in NSP2 of Chikungunya virus: An in-silico approach

Fazal F, Anwar T, Waheed Y, Parvaiz F

Trop Biomed, 2020 Sep 01;37(3):566-577.
PMID: 33612772 DOI: 10.47665/tb.37.3.566

This study is focused towards developing a global consensus sequence of nonstructural protein 2 (NSP2), a protease of Chikungunya Virus (CHIKV) and predict immunogenic promiscuous T-cell epitopes based on various bioinformatics tools. To date, no epitope data is available for the Chikungunya virus in the IEDB database. In this study, 100 available nucleotide sequences of NSP2-CHIKV belonging to different strains were downloaded from the National Centre for Biotechnology Information (NCBI) database. The nucleotide sequences were subjected to translated sequencing using the EXPASY tool followed by protein alignment using the CLC workbench and a global consensus sequence for the respective protein was developed. IEDB tool was used to predict HLA-I and HLA-II binding promiscuous epitopes from the consensus sequence of NSP2-CHIKV. Thirty-four B-cell based epitopes are predicted and the promiscuous epitope is VVDTTGSTKPDPGD at position 341-354. Twenty-six MHC-I short peptide epitopes are predicted to bind with HLA-A. The promiscuous epitopes predicted to bind with HLA-A*01:01 are VTAIVSSLHY, SLSESATMVY, FSKPLVYY, QPTDHVVGEY at positions 317-326, 84-93, 535-544 and 15-24 with percentile ranks 0.17, 0.39, 0.51 and 0.81, respectively. Twenty-four MHC-II short peptide epitopes are predicted for HLA-DRB. The promiscuous epitope predicted to bind with HLA-DRB*01:01 is VVGEYLVLSPQTVLRS from 20-35 with a lowest percentile rank of 0.01. These predicted epitopes can be effective targets towards development of vaccine against CHIKV. Epitopes predicted in this study displayed good binding affinity, antigenicity and promiscuity for the HLA classes. These predicted epitopes can prove to be translationally important towards the development of CHIKV.

Matched MeSH terms: Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte
Fulltext Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes

Hasan NH, Ebrahimie E, Ignjatovic J, Tarigan S, Peaston A, Hemmatzadeh F

PLoS One, 2016;11(6):e0156418.
PMID: 27362795 DOI: 10.1371/journal.pone.0156418

A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e) protein of avian influenza virus (AIV) as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA) is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs) recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb) and chicken antibodies (cAbs) recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development.

Matched MeSH terms: Epitopes/immunology*
Fulltext The neutralizing role of IgM during early Chikungunya virus infection

Chua CL, Sam IC, Chiam CW, Chan YF

PLoS One, 2017;12(2):e0171989.
PMID: 28182795 DOI: 10.1371/journal.pone.0171989

The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays.

Matched MeSH terms: Epitopes/immunology
Epitope variances demonstrated by Blastocystis sp. ST3 symptomatic and asymptomatic isolates

Sheela DS, Chandramathi S, Suresh K

Trop Biomed, 2020 Mar 01;37(1):210-217.
PMID: 33612732

Blastocystis sp. is an enteric protozoan parasite of humans and many animals. Blastocystis sp. subtype 3 (ST3) proves to be the highest frequency case in most populations around the world and it is further distinguished into symptomatic and asymptomatic isolates based on the clinical symptoms exhibited by infected individuals. Phenotypic and genotypic studies implicate the distinctiveness of this parasite which may describe its pathogenesis. However, the antigenic distinctiveness which describes the antibody mediated cell lysis of this parasite has not been explored. This study was aimed to identify the cross-reactivity and cytotoxicity effect between three isolates of symptomatic and asymptomatic Blastocystis sp. ST3 respectively. Antigen specificity and diversity of this parasite was performed by coculturing sera (10-fold dilution) obtained from mice immunised with Blastocystis sp. symptomatic and asymptomatic antigens and the respective Blastocystis sp. ST3 live cells through complement dependant cell cytotoxicity (CDC) assay. The results obtained has shown that, the sera (at 10-fold diluted concentration) from symptomatic and asymptomatic solubilised antigen immunised mice were able to specifically lyse the respective live parasites with an average percentage of 82% and 86% respectively. There were almost 50% crossreactivity observed between the three isolates of Blastocystis sp. ST3 from symptomatic and asymptomatic group proving high antigen diversity or rather low antigen specificity within the same group. However, there was only 17% cross-reactivity observed between the mice sera and parasitic cells of different groups (symptomatic vs asymptomatic isolates) suggesting high specificity between these two groups. We, for the first time have proven that through CDC analysis there were epitopes dissimilarities between Blastocystis sp. ST3 symptomatic and asymptomatic isolates which may allow the parasite to set up diverse immune modulations such as imbalanced Th1/Th2 responses in an infected host.

Matched MeSH terms: Epitopes/immunology*
Localization of the antigenic sites of newcastle disease virus nucleocapsid using a panel of monoclonal antibodies

Ahmad-Raus R, Ali AM, Tan WS, Salleh HM, Eshaghi M, Yusoff K

Res Vet Sci, 2009 Feb;86(1):174-82.
PMID: 18599098 DOI: 10.1016/j.rvsc.2008.05.013

A panel of six monoclonal antibodies (mAbs) against the nucleocapsid (NP) protein of Newcastle disease virus (NDV) was produced by immunization of Balb/c mice with purified recombinant NP protein. Western Blot analysis showed that all the mAbs recognized linearized NP epitopes. Three different NP antigenic sites were identified using deleted truncated NP mutants purified from Escherichia coli. One of the antigenic sites was located at the C-terminal end (residues 441 to 489) of the NP protein. Two other antigenic sites were located within the N-terminal end (residues 26-121 and 122-375). This study demonstrates that the N- and C-terminal ends of the NP proteins are responsible in eliciting immune response, thus it is most likely that these ends are exposed on the NP.

Matched MeSH terms: Epitopes/immunology
An immunogenic epitope of Chlamydia pneumoniae from a random phage display peptide library is reactive with both monoclonal antibody and patients sera

Naidu BR, Ngeow YF, Wang LF, Chan L, Yao ZJ, Pang T

Immunol Lett, 1998 Jun;62(2):111-5.
PMID: 9698107

Random 15-mer peptides displayed on filamentous phages were screened in binding studies using a Chlamydia pneumoniae-specific monoclonal antibody (RR-402) and affinity-purified, polyclonal sera from patients seropositive for C. pneumoniae infections by the microimmunofluorescence (MIF) test. One 15-mer epitope, epitope Cpnl5A (LASLCNPKPSDAPVT) was identified in both the monoclonal and polyclonal screenings, and showed higher ELISA reactivity with C. pneumoniae MIF-positive sera compared to patients with other chlamydial infections, non-chlamydial respiratory infections and normal healthy sera (MIF-negative). Interestingly, epitope Cpnl5A also showed significant (52%) amino acid sequence homology to the 56 kDa type-specific antigen of Rickettsia tsutsugamushi, a protein implicated in the virulence of this organism.

Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*
Fulltext Structural Evaluation of the Spike Glycoprotein Variants on SARS-CoV-2 Transmission and Immune Evasion

Salleh MZ, Derrick JP, Deris ZZ

Int J Mol Sci, 2021 Jul 10;22(14).
PMID: 34299045 DOI: 10.3390/ijms22147425

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Matched MeSH terms: Epitopes, B-Lymphocyte/immunology
Evaluation of neutralizing antibodies produced by papaya mosaic virus nanoparticles fused to the E2EP3 peptide epitope of Chikungunya envelope

Nor Rashid N, Teoh TC, Al-Harbi SJ, Yusof R, Rothan HA

Trop Biomed, 2021 Mar 01;38(1):36-41.
PMID: 33797522 DOI: 10.47665/tb.38.1.007

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV-C- E2EP3, and E2EP3-N-PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3-N-PapMV and PapMVC-E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3-N-PapMV or PapMV-C-E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.

Matched MeSH terms: Epitopes/immunology
Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant

Azmi F, Ahmad Fuaad AA, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al.

Bioorg Med Chem, 2014 Nov 15;22(22):6401-8.
PMID: 25438764 DOI: 10.1016/j.bmc.2014.09.042

Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.

Matched MeSH terms: Epitopes/immunology; Epitopes/chemistry
High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1

Tan CS, Cardosa MJ

Arch Virol, 2007;152(6):1069-73.
PMID: 17318736

Human enterovirus 71 has emerged as an important pathogen of children in the Asia Pacific region, and it may be important to consider the development of a vaccine against this virus. Human cord serum was used as a source of neutralizing antibodies to determine whether the N- or C-terminal half of the VP1 capsid protein was more likely to harbour neutralizing determinants. Cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect ELISA against recombinant VP1 antigen as well as the N- and C-terminal portions of VP1 antigen. High-titred human neutralizing antibodies were significantly more reactive with the N-terminal half of VP1 than weak or negative sera. The N-terminal half of human enterovirus 71 is likely to have important neutralizing antibody determinants and should be investigated further in vaccine development efforts.

Matched MeSH terms: Epitopes/genetics; Epitopes/chemistry
Research note: HLA degenerate T-cell epitopes from Plasmodium falciparum liver stage-specific antigen 1 (LSA-1) are highly conserved in isolates from geographically distinct areas

Ravichandran M, Doolan DL, Cox-Singh J, Hoffman SL, Singh B

Parasite Immunol., 2000 Sep;22(9):469-73.
PMID: 10972854

Considerable effort is directed at the development of a malaria vaccine that elicits antigen-specific T-cell responses against pre-erythrocytic antigens of Plasmodium falciparum. Genetic restriction of host T-cell responses and polymorphism of target epitopes on parasite antigens pose obstacles to the development of such a vaccine. Liver stage-specific antigen-1 (LSA-1) is a prime candidate vaccine antigen and five T-cell epitopes that are degenerately restricted by HLA molecules common in most populations have been identified on LSA-1. To define the extent of polymorphism within these T-cell epitopes, the N-terminal non-repetitive region of the LSA-1 gene from Malaysian P. falciparum field isolates was sequenced and compared with data of isolates from Brazil, Kenya and Papua New Guinea. Three of the T-cell epitopes were completely conserved while the remaining two were highly conserved in the isolates examined. Our findings underscore the potential of including these HLA-degenerate T-cell epitopes of LSA-1 in a subunit vaccine.

Matched MeSH terms: Epitopes, T-Lymphocyte/genetics*; Epitopes, T-Lymphocyte/immunology*
Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia

Tarone RE, Levine PH, Yadav M, Pandey JP

Cancer Res, 1990 Jun 1;50(11):3186-8.
PMID: 1692255

The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.

Matched MeSH terms: Epitopes/genetics*; Epitopes/immunology
Fulltext Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.

Vaccine, 2018 03 27;36(14):1853-1862.
PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065

Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.

Matched MeSH terms: Epitopes/immunology; Epitopes/chemistry

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