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

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.

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Measurement over 1 Year of Neutralizing Antibodies in Cattle Immunized with Trivalent Vaccines Recombinant Alpha, Beta and Epsilon of Clostridium perfringens

Toxins ◽

10.3390/toxins13090594 ◽

2021 ◽

Vol 13 (9) ◽

pp. 594

Author(s):

Cleideanny C. Galvão ◽

José D. Barbosa ◽

Carlos M. C. Oliveira ◽

Denis Y. Otaka ◽

Paulo R. O. Silva ◽

...

Keyword(s):

Immune Response ◽

Clostridium Perfringens ◽

Recombinant Proteins ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Scale Production ◽

Humoral Immune ◽

Antibody Titers ◽

Production Animals

The alpha (CPA), beta (CPB) and epsilon (ETX) toxins of Clostridium perfringens are responsible for causing diseases that are difficult to eradicate and have lethal potential in production animals. Vaccination of herds is still the best control strategy. Recombinant clostridial vaccines have shown good success at inducing neutralizing antibody titers and appear to be a viable alternative to the conventional production of commercial clostridial toxoids. Research is still needed on the longevity of the humoral immune response induced by recombinant proteins in immunized animals, preferably in target species. The objective of this study was to measure the humoral immune response of cattle immunized with trivalent vaccines containing the recombinant proteins alpha (rCPA), beta (rCPB) and epsilon (rETX) of C. perfringens produced in Escherichia coli at three different concentrations (100, 200, and 400 µg) of each protein for 12 months. The recombinant vaccines containing 200 (RV2) and 400 µg (RV3) yielded statistically similar results at 56 days. They performed better throughout the study period because they induced higher neutralizing antibody titers and were detectable for up to 150 and 180 days, respectively. Regarding industrial-scale production, RV2 would be the most economical and viable formulation as it achieved results similar to RV3 at half the concentration of recombinant proteins in its formulation. However, none of the vaccines tested induced the production of detectable antibody titers on day 365 of the experiment, the time of revaccination typically recommended in vaccination protocols. Thus, reiterating the need for research in the field of vaccinology to achieve greater longevity of the humoral immune response against these clostridial toxins in animals, in addition to the need to discuss the vaccine schedules and protocols adopted in cattle production.

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

Journal of Virology ◽

10.1128/jvi.01711-08 ◽

2009 ◽

Vol 83 (7) ◽

pp. 3228-3237 ◽

Cited By ~ 34

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.

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Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing antibody titers in bovines

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821998000400006 ◽

1998 ◽

Vol 31 (4) ◽

pp. 367-371 ◽

Cited By ~ 5

Author(s):

Avelino Albas ◽

Paulo Eduardo Pardo ◽

Albério Antonio Barros Gomes ◽

Fernanda Bernardi ◽

Fumio Honma Ito

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Booster Dose ◽

Neutralization Test ◽

Neutralizing Antibody ◽

Rabies Vaccine ◽

Western Region ◽

Humoral Immune ◽

Paulo State ◽

Antibody Titers

Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers 30.5IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%), with titers 30.5IU/ml and at 360 days, 4 (19.0%), with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00443-15 ◽

2015 ◽

Vol 22 (12) ◽

pp. 1235-1243 ◽

Cited By ~ 9

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.

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Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies

Transfusion Medicine and Hemotherapy ◽

10.1159/000515610 ◽

2021 ◽

pp. 1-10

Author(s):

Sixten Körper ◽

Bernd Jahrsdörfer ◽

Victor M. Corman ◽

Jan Pilch ◽

Patrick Wuchter ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Controlled Clinical Trial ◽

Neutralizing Capacity ◽

Iga Antibodies ◽

Antibody Titers ◽

Antibody Levels ◽

Over Time

Background: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. Methods: Patients who had recovered from COVID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. Results: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. Conclusion: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

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Clinicogenomic analysis of breakthrough infections by SARS CoV2 variants after ChAdOx1 nCoV- 19 vaccination in healthcare workers

10.1101/2021.06.28.21259546 ◽

2021 ◽

Author(s):

Pratibha Kale ◽

Ekta Gupta ◽

Chhagan Bihari ◽

Niharika Patel ◽

Sheetalnath Rooge ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Genomic Analysis ◽

Hospital Staff ◽

Risk Of Infection ◽

Rt Pcr ◽

Humoral Immune ◽

Antibody Levels

Background: India saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs). Methods: The study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV- 19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS). Results: Infection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p <0.001) than 9.52% (156/1639) vaccinated group. VBT infections were significantly higher in doctors and nurses compared to other hospital staff (p <0.001). Unvaccinated individuals had 1.57 times higher risk of infection compared to partially vaccinated (p 0.02) and 2.49 times than fully vaccinated (<0.001). Partially vaccinated were at higher risk of infection than fully vaccinated (RR 1.58,p 0.01). There were 3 (1.36%) severe cases and 1 death in unvaccinated group compared to none in the vaccinated. Non-response after 14 days of second dose was seen in 6.5% (3/46) and low antibody levels (1-4.62 S/CO) in 8.69% (4/46). Delta variant (B.1.617.2) was dominant (69.5%) and reinfection was documented in 4 (0.06%) HCWs. Conclusions: Nearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.

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Maternally Derived Antibody Levels Influence on Vaccine Protection against PCV2d Challenge

Animals ◽

10.3390/ani11082231 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2231

Author(s):

István Kiss ◽

Krisztina Szigeti ◽

Zalán G. Homonnay ◽

Vivien Tamás ◽

Han Smits ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Subunit Vaccine ◽

Porcine Circovirus Type ◽

Porcine Circovirus ◽

Vaccine Protection ◽

Humoral Immune ◽

Negative Effect ◽

Antibody Levels

Piglets from a porcine circovirus type 2 (PCV2) stable farm of low and high levels of maternally derived antibodies (MDA) against PCV2 were vaccinated either with a whole virus type or a PCV2 ORF2 antigen-based commercial subunit vaccine at three weeks of age. Two non-vaccinated groups served as low and high MDA positive controls. At four weeks post vaccination, all piglets were challenged with a PCV2d-2 type virus strain and were checked for parameters related to vaccine protection over a four-week observation period. MDA levels evidently impacted the outcome of the PCV2d-2 challenge in non-vaccinated animals, while it did not have a significant effect on vaccine-induced protection levels. The humoral immune response developed faster in the whole virus vaccinates than in the subunit vaccinated pigs in the low MDA groups. Further, high MDA levels elicited a stronger negative effect on the vaccine-induced humoral immune response for the subunit vaccine than for the whole virus vaccine. The group-based oral fluid samples and the group mean viraemia and faecal shedding data correlated well, enabling this simple, and animal welfare-friendly sampling method for the evaluation of the PCV2 viral load status of these nursery piglets.

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Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽

10.3390/v13020284 ◽

2021 ◽

Vol 13 (2) ◽

pp. 284

Author(s):

Hulda R. Jonsdottir ◽

Michel Bielecki ◽

Denise Siegrist ◽

Thomas W. Buehrer ◽

Roland Züst ◽

...

Keyword(s):

Young Adults ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Humoral Response ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Asymptomatic Infection ◽

Homogeneous Population ◽

Humoral Immune ◽

Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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