scholarly journals The Porcine Humoral Immune Response against Pseudorabies Virus Specifically Targets Attachment Sites on Glycoprotein gC

2000 ◽  
Vol 74 (4) ◽  
pp. 1752-1760 ◽  
Author(s):  
Bertram T. Ober ◽  
Berthold Teufel ◽  
Karl-Heinz Wiesmüller ◽  
Günther Jung ◽  
Eberhard Pfaff ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Pseudorabies Virus ◽  
Host Protein ◽  
Target Cells ◽  
Heparin Binding ◽  
Viral Attachment ◽  
Neutralizing Activity ◽  
Humoral Immune

ABSTRACT High titers of virus-neutralizing antibodies directed against glycoprotein gC of Pseudorabies virus (PRV) (Suid herpesvirus 1) are generally observed in the serum of immunized pigs. A known function of the glycoprotein gC is to mediate attachment of PRV to target cells through distinct viral heparin-binding domains (HBDs). Therefore, it was suggested that the virus-neutralizing activity of anti-PRV sera is directed against HBDs on gC. To address this issue, sera with high virus-neutralizing activity against gC were used to characterize the anti-gC response. Epitope mapping demonstrated that amino acids of HBDs are part of an antigenic antibody binding domain which is located in the N-terminal part of gC. Binding of antibodies to this antigenic domain of gC was further shown to interfere with the viral attachment. Therefore, these results show that the viral HBDs are accessible targets for the humoral anti-PRV response even after tolerance induction against self-proteins, which utilize similar HBDs to promote host protein-protein interactions. The findings indicate that the host's immune system can specifically block the attachment function of PRV gC. Since HBDs promote the attachment of a number of herpesviruses, the design of future antiherpesvirus vaccines should aim to induce a humoral immune response that prevents HBD-mediated viral attachment.

scholarly journals Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

Cell Research ◽  
2021 ◽  
Author(s):  
Yunlong Cao ◽  
Ayijiang Yisimayi ◽  
Yali Bai ◽  
Weijin Huang ◽  
Xiaofeng Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Immune Escape ◽  
Natural Infection ◽  
Peripheral Blood Mononuclear ◽  
Neutralizing Activity ◽  
Humoral Immune ◽  
Complementarity Determining Regions

AbstractSARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242–244 deletion (242–244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242–244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

scholarly journals Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles

2009 ◽  
Vol 83 (7) ◽  
pp. 3228-3237 ◽  
Author(s):  
François-Loic Cosset ◽  
Philippe Marianneau ◽  
Geraldine Verney ◽  
Fabrice Gallais ◽  
Noel Tordo ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Cell Attachment ◽  
Low Ph ◽  
Cell Entry ◽  
Lassa Virus ◽  
Ph Optimum ◽  
Humoral Immune

ABSTRACT The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.

scholarly journals Comparison of gE/gI- and TK/gE/gI-Gene-Deleted Pseudorabies Virus Vaccines Mediated by CRISPR/Cas9 and Cre/Lox Systems

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 369
Author(s):  
Jianglong Li ◽  
Kui Fang ◽  
Zhenxiang Rong ◽  
Xinxin Li ◽  
Xujiao Ren ◽  
...  
Keyword(s):  
Immune Response ◽  
Cd8 T Cells ◽  
Humoral Immune Response ◽  
Pseudorabies Virus ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Humoral Immune ◽  
Viral Shedding ◽  
Ifn Γ ◽  
Efficacious Vaccine

Pseudorabies (PR), caused by pseudorabies virus (PRV), is an acute and febrile infectious disease in swine. To eradicate PR, a more efficacious vaccine needs to be developed. Here, the gE/gI- and TK/gE/gI-gene-deleted recombinant PRV (rGXΔgE/gI and rGXΔTK/gE/gI) are constructed through CRISPR/Cas9 and Cre/Lox systems. We found that the rGXΔTK/gE/gI was safer than rGXΔgE/gI in mice. Additionally, the effects of rGXΔgE/gI and rGXΔTK/gE/gI were further evaluated in swine. The rGXΔgE/gI and rGXΔTK/gE/gI significantly increased numbers of IFN-γ-producing CD4+ and CD8+ T-cells in swine, whereas there was no difference between rGXΔgE/gI and rGXΔTK/gE/gI. Moreover, rGXΔgE/gI and rGXΔTK/gE/gI promoted a PRV-specific humoral immune response. The PRV-specific humoral immune response induced by rGXΔgE/gI was consistent with that caused by rGXΔTK/gE/gI. After the challenge, swine vaccinated with rGXΔgE/gI and rGXΔTK/gE/gI showed no clinical signs and viral shedding. However, histopathological detection revealed that rGXΔgE/gI, not rGXΔTK/gE/gI, caused pathological lesions in brain and lung tissues. In summary, these results demonstrate that the TK/gE/gI-gene-deleted recombinant PRV was safer compared with rGXΔgE/gI in swine. The data imply that the TK/gE/gI-gene-deleted recombinant PRV may be a more efficacious vaccine candidate for the prevention of PR.

scholarly journals Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

2015 ◽  
Vol 22 (12) ◽  
pp. 1235-1243 ◽  
Author(s):  
Andrew C. Y. Lee ◽  
Houshun Zhu ◽  
Anna J. X. Zhang ◽  
Can Li ◽  
Pui Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Case Fatality ◽  
H7n9 Virus ◽  
Humoral Immune ◽  
Homologous Virus ◽  
Antibody Titers

ABSTRACTInfluenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus.

scholarly journals Replication of Beta- and Gammaretroviruses Is Restricted in I/LnJ Mice via the Same Genetic Mechanism

2007 ◽  
Vol 82 (3) ◽  
pp. 1438-1447 ◽  
Author(s):  
Laure K. Case ◽  
Lydia Petell ◽  
Leonid Yurkovetskiy ◽  
Alexandra Purdy ◽  
Katherine J. Savage ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Leukemia Virus ◽  
Resistance Mechanism ◽  
Recessive Gene ◽  
Chromosome 17 ◽  
Interleukin 12 ◽  
Chromosome 15 ◽  
Humoral Immune

ABSTRACT Mice of the I/LnJ inbred strain are unique in their ability to mount a robust and sustained humoral immune response capable of neutralizing infection with a betaretrovirus, mouse mammary tumor virus (MMTV). Virus-neutralizing antibodies (Abs) coat MMTV virions secreted by infected cells, preventing virus spread and hence the formation of mammary tumors. To investigate whether I/LnJ mice resist infection with other retroviruses besides MMTV, the animals were infected with murine leukemia virus (MuLV), a gammaretrovirus. MuLV-infected I/LnJ mice produced virus-neutralizing Abs that block virus transmission and virally induced disease. Generation of virus-neutralizing Abs required gamma interferon but was independent of interleukin-12. This unique mechanism of retrovirus resistance is governed by a single recessive gene, virus infectivity controller 1 (vic1), mapped to chromosome 17. In addition to controlling the antivirus humoral immune response, vic1 is also required for an antiviral cytotoxic response. Both types of responses were maintained in mice of the susceptible genetic background but congenic for the I/LnJ vic1 locus. Although the vic1-mediated resistance to MuLV resembles the mechanism of retroviral recovery controlled by the resistance to Friend virus 3 (rfv3) gene, the rfv3 gene has been mapped to chromosome 15 and confers resistance to MuLV but not to MMTV. Thus, we have identified a unique virus resistance mechanism that controls immunity against two distinct retroviruses.

scholarly journals Sequential Changes in the Humoral Immune Response of Pigs to Pseudorabies Virus after Vaccination, Exposure to Virulent Virus, and Reactivation of Latent Virus

1990 ◽  
Vol 2 (1) ◽  
pp. 35-43 ◽  
Author(s):  
William L. Mengeling ◽  
Eugene C. Pirtle
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Pseudorabies Virus ◽  
Viral Proteins ◽  
Latent Virus ◽  
Virus Reactivation ◽  
Dexamethasone Treatment ◽  
Humoral Immune ◽  
Attenuated Virus ◽  
Virulent Virus

Sequential changes in the humoral immune response of pigs to pseudorabies virus (PRV) after each of several exposures to the virus were evaluated by determining virus neutralization (VN) and radioimmunoprecipitation (RIP) activities of sera collected at selected intervals. Pigs were vaccinated intramuscularly with live attenuated virus (6 pigs), inactivated attenuated virus (6 pigs), or inactivated virulent virus (6 pigs). All pigs were challenged oronasally with virulent virus 3 weeks later and 12 (4 pigs of each vaccine group) were subsequently treated with dexamethasone in an attempt to reactivate latent virus. The relatively low serum titers of VN antibody that were raised by vaccination (titers ranged from 2 to 32) increased markedly (at least 16-fold) for all pigs after exposure to virulent virus. After dexamethasone treatment, the VN titers of 2 pigs increased 16-fold, whereas those of the other 10 dexamethasone-treated pigs and the 6 nontreated pigs either remained the same or increased only minimally (i.e., no more than 2-fold). The results of RIP using 35S-methionine-labeled viral proteins were initially similar to those of VN in that the low levels of serum RIP activity detected after vaccination increased markedly after subsequent exposure to virulent virus. In contrast to VN, however, most pigs (11 of 12) treated with dexamethasone had a clear increase in serum RIP activity. The increase was particularly striking for viral proteins of relatively low (<46K) molecular weight. Precipitating activity for 14C-glucosamine-labeled viral glycoproteins was not detected until after pigs were exposed to virulent virus. The increase in RIP activity detected after dexamethasone treatment was likely due to an additional antigenic stimulus associated with virus reactivation. However, virus was isolated from nasal swabs of only 4 of the 12 treated pigs. None of the results appeared to be affected appreciably by the type of vaccine used for initial immunization.

scholarly journals Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers

Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Pratibha Kale ◽  
Ekta Gupta ◽  
Chhagan Bihari ◽  
Niharika Patel ◽  
Sheetalnath Rooge ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Genomic Analysis ◽  
Whole Genome ◽  
Humoral Immune

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

scholarly journals Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV)

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 880 ◽  
Author(s):  
Gökce Nur Cagatay ◽  
Denise Meyer ◽  
Michael Wendt ◽  
Paul Becher ◽  
Alexander Postel
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Humoral Immune ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Congenital Tremor

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.

scholarly journals Clinical and Serological Evaluation of LINDA Virus Infections in Post-Weaning Piglets

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 975 ◽  
Author(s):  
Alexandra Kiesler ◽  
Kerstin Seitz ◽  
Lukas Schwarz ◽  
Katharina Buczolich ◽  
Helga Petznek ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Post Infection ◽  
Neutralizing Antibodies ◽  
Intrauterine Infection ◽  
Virus Infections ◽  
Virus Shedding ◽  
Humoral Immune ◽  
Successful Replication ◽  
Weaning Piglets

The novel pestivirus species known as lateral-shaking inducing neuro-degenerative agent (LINDA) virus emerged in 2015 in a piglet-producing farm in Austria. Affected piglets showed strong congenital tremor as a result of severe lesions in the central nervous system. Here, we report the results of a controlled animal infection experiment. Post-weaning piglets were infected with LINDA to determine the susceptibility of pigs, the clinical consequences of infection and the humoral immune response against LINDA. No clinically overt disease signs were observed in the piglets. Viremia was hardly detectable, but LINDA was present in the spleen and several lymphatic organs until the end of the experiment on day 28 post-infection. Oronasal virus shedding together with the infection of one sentinel animal provided additional evidence for the successful replication and spread of LINDA in the piglets. Starting on day 14 post-infection, all infected animals showed a strong humoral immune response with high titers of neutralizing antibodies against LINDA. No cross-neutralizing activity of these sera with other pestiviral species was observed. According to these data, following postnatal infection, LINDA is a rather benign virus that can be controlled by the pig’s immune system. However, further studies are needed to investigate the effects of LINDA on the fetus after intrauterine infection.

scholarly journals Rarely Recognized Antibody Diversification in Covid-19 Evolution to Counteract Advanced SARS-CoV-2 Evasion Strategies, and Implications for Prophylactic Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Siguna Mueller
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Prophylactic Treatment ◽  
Natural Infection ◽  
Rapid Development ◽  
Disease Evolution ◽  
Humoral Immune ◽  
Antibody Diversification ◽  
Cell Immunity

The ongoing Covid-19 pandemic underscores the importance of finding effective and safe ways to combat the virus, and to optimally understand the immune response elicited upon natural infection. This likely involves all components of the immune system, both innate and adaptive. The impetus for the rapid development of prophylactic treatment options has led to an intense focus on neutralizing antibodies (Abs), and many novel and specialized platforms have been designed to achieve that goal. B-cell immunity relies on the generation of a diverse repertoire of Abs. Their structural variation is defined in terms of amino acid composition that is encoded in the genome or acquired through somatic mutations. Yet, key examples of frequently neglected antibody diversification mechanisms involving post-translational modifications such as N- or O-linked glycosylation are present in significant portions of the population. During the last few years, these and other beyond gene sequence determined humoral immune response mechanisms have in some specific cases revealed their potent immunomodulatory effects. Nonetheless, such more unusual mechanisms have not received much attention in the context of SARS-CoV-2. Thus, with specific focus on the latter, this paper presents, (1) the rationale for considering beyond sequence determined strategies, (2) evidence for their possible involvement in Covid-19 disease evolution, (3) consequences for vaccine design exemplified by one of the vaccine candidates that is currently undergoing trial, and (4) more general implications. Based on a critical interpretation of published literature, the hypotheses developed in this study point to a crucial role of non-genetic antibody diversification mechanisms in disease evolution to counteract unique immunogenicity determinants of SARS-CoV-2 infection. The involvement of post translational mechanisms may also help explain the widely varied immune response observed, not only among different patient groups, but also in terms of their observed incompatibility with SARS-CoV-2 infection in several human cell types. The article highlights potentials and challenges of these refined humoral immune response mechanisms to most optimally target non-genetic viral evasion strategies.

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