Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD “In-House” ELISA

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) challenges health systems to quickly respond by developing new diagnostic strategies that contribute to identify infected individuals, monitor infections, perform contact-tracing, and limit the spread of the virus. In this brief report, we developed a highly sensitive, specific, and precise “In-House” ELISA to correctly discriminate previously SARS-CoV-2-infected and non-infected individuals and study population seroprevalence. Among 758 individuals evaluated for anti-SARS-CoV-2 serology in the province of Tucumán, Argentina, we found a weak correlation between antibodies elicited against the RBD, the receptor-binding domain of the Spike protein, and the nucleocapsid (N) antigens of this virus. Additionally, we detected mild levels of anti-RBD IgG antibodies in 33.6% of individuals diagnosed with COVID-19, while only 19% showed sufficient antibody titers to be considered as plasma donors. No differences in IgG anti-RBD titers were found between women and men, neither in between different age groups ranging from 18 to 60. Surprisingly, individuals from a high altitude village displayed elevated and longer lasting anti-RBD titers compared to those from a lower altitude city. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-CoV-2 infection.

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An “In-House” ELISA for SARS-CoV-2 RBD uncovers elevated immune response at higher altitudes

10.1101/2021.03.10.21252711 ◽

2021 ◽

Author(s):

Tomas Grau Rodrigo ◽

Ploper Diego ◽

Ávila César ◽

Vera Pingitore Esteban ◽

Maldonado Carolina ◽

...

Keyword(s):

Immune Response ◽

Protective Factor ◽

Serological Test ◽

Pearson Correlation ◽

High Sensitivity ◽

Igg Antibodies ◽

Lower Altitude ◽

Humoral Immune ◽

Global Pandemic ◽

Antibody Titers

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first reported in Wuhan has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) associated represents a challenge for health systems that had to quickly respond developing new diagnostic and therapeutic strategies. In the present work, we developed an “In House” ELISA with high sensitivity (92.2 %), specificity (100%) and precision (93.9%), with an area under the ROC curve (AUC) of 0.991, rendering the assay as an excellent serological test to correctly discriminate between SARS-COv-2 infected and non-infected individuals and study population seroprevalence. Among 758 patients evaluated for SARS-CoV-2 diagnosis in the province of Tucumán, Argentina, we found a Pearson correlation coefficient of 0.5048 between antibodies elicited against the RBD and the nucleocapsid (N) antigen. Additionally, 33.6% of individuals diagnosed with COVID-19 displayed mild levels of RBD-IgG antibodies, while 19% of the patients showed high antibody titers. Interestingly, patients with SARS-COV-2 infection over 60 years old elicited significantly higher levels of IgG antibodies against RBD compared to younger ones, while no difference was found between women and men. Surprisingly, individuals from a high altitude village displayed statistically significant higher and longer lasting anti-RBD antibodies compared to those from a city at a lower altitude, suggesting that a hypobaric hypoxia-adapted mechanism may act as a protective factor for COVID-19. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-Cov-2 infection.

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Bordetella pertussis Filamentous Hemagglutinin Enhances the Immunogenicity of Liposome-Delivered Antigen Administered Intranasally

Infection and Immunity ◽

10.1128/iai.66.4.1764-1767.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1764-1767 ◽

Cited By ~ 14

Author(s):

Odile Poulain-Godefroy ◽

Nathalie Mielcarek ◽

Nathalie Ivanoff ◽

Franck Remoué ◽

Anne-Marie Schacht ◽

...

Keyword(s):

Immune Response ◽

Bordetella Pertussis ◽

Humoral Immune Response ◽

Dependent Manner ◽

Humoral Immune ◽

Filamentous Hemagglutinin ◽

Antibody Titers ◽

Suboptimal Dose ◽

Outbred Mice ◽

Dose Dependent

ABSTRACT In an attempt to increase the immunogenicity of mucosally delivered antigens, we incorporated the Bordetella pertussisfilamentous hemagglutinin (FHA) adhesin into liposomes containing the glutathione S-transferase of Schistosoma mansoni (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with liposomes containing a constant suboptimal dose of Sm28GST and increasing doses of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The addition of 3 μg of FHA to the liposomes induced more than 10-fold-higher anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA. The presence of FHA did not alter the nature of the humoral immune response, and the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b. However, anti-Sm28GST IgA was only detected when at least 3 μg of FHA was added to the preparation. These results show a promising potential for FHA to enhance the immunogenicity of mucosally administered antigens incorporated into liposomes.

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Typically asymptomatic but with robust antibody formation: Childrens unique humoral immune response to SARS-CoV-2

10.1101/2021.07.20.21260863 ◽

2021 ◽

Author(s):

Hanna Renk ◽

Alex Dulovic ◽

Matthias Becker ◽

Dorit Fabricius ◽

Maria Zernickel ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Age Groups ◽

Asymptomatic Infection ◽

Serological Response ◽

Vaccination Programs ◽

Humoral Immune ◽

Viral Spread ◽

Antibody Assays

Background: Long-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children's natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV-2 vaccination programs. Methods: In this prospective observational multi-center cohort study, we followed 328 households, consisting of 548 children and 717 adults, with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. The serological response was assessed at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Results: Overall, 33.76% of SARS-CoV-2 exposed children and 57.88% adults were seropositive. Children were five times more likely to have seroconverted without symptoms compared to adults. Despite the frequently asymptomatic course of infection, children had higher specific antibody levels, and their antibodies persisted longer than in adults (96.22% versus 82.89% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induced similar humoral responses in all age groups. In symptomatic children, only dysgeusia was found as diagnostic indicator of COVID-19. SARS-CoV-2 infections occurred independent of HCoV serostatus. Antibody binding responses to VOCs were similar in children and adults, with reduced binding for the Beta variant in both groups. Conclusions: The long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection. (Study ID at German Clinical Trials Register: 00021521)

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Robust and durable serological response following pediatric SARS-CoV-2 infection

Nature Communications ◽

10.1038/s41467-021-27595-9 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Hanna Renk ◽

Alex Dulovic ◽

Alina Seidel ◽

Matthias Becker ◽

Dorit Fabricius ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Age Groups ◽

Asymptomatic Infection ◽

Pseudotyped Virus ◽

Serological Response ◽

Vaccination Programs ◽

Humoral Immune ◽

Antibody Assays ◽

Human Coronaviruses

AbstractThe quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3–4 months and 11–12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11–12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

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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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Characterization of the Humoral Immune Response to Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Infection

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063879500700302 ◽

1995 ◽

Vol 7 (3) ◽

pp. 305-312 ◽

Cited By ~ 118

Author(s):

Kyoung-Jin Yoon ◽

Jeffrey J. Zimmerman ◽

Sabrina L. Swenson ◽

Michael J. McGinley ◽

Ken A. Eernisse ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Fluorescent Antibody ◽

Viral Proteins ◽

Immunoblot Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Prrs Virus ◽

Humoral Immune ◽

Antibody Titers ◽

Rate Of Decline

The development of the humoral immune response against porcine reproductive and respiratory syndrome (PRRS) virus was monitored by an indirect fluorescent antibody (IFA) test, immunoperoxidase monolayer assay (IPMA), enzyme-linked immunosorbent assay (ELISA), and serum virus neutralization (SVN) test over a 105-day period in 8 pigs experimentally infected with ATCC strain VR-2402. Specific antibodies against PRRS virus were first detected by the IFA test, IPMA, ELISA, and the SVN test 9-11, 5-9, 9-13, and 9-28 days postinoculation (PI), respectively, and reached their maximum values by 4-5, 5-6, 4-6, and 10-11 weeks PI, respectively, thereafter. After reaching maximum value, all assays showed a decline in antibody levels. Assuming a constant rate of antibody decay, it was estimated by regression analysis that the ELISA, IFA, IPMA, and SVN antibody titers would approach the lower limits of detection by approximately days 137, 158, 324, and 356 PI, respectively. In this study, the immunoperoxidase monolayer assay appeared to offer slightly better performance relative to the IFA test, ELISA, and SVN test in terms of earlier detection and slower rate of decline in antibody titers. Western immunoblot analysis revealed that antibody specific for the 15-kD viral protein was present in all pigs by 7 days PI and persisted throughout the 105-day observation period. Initial detection of antibodies to the 19-, 23-, and 26-kD proteins varied among pigs, ranging from 9 to 35 days PI. Thereafter, the antibody responses to these 3 viral proteins of PRRS virus continued to be detected throughout the 105-day study period. These results clearly indicate that the 15-kD protein is the most immunogenic of the 4 viral proteins identified and may provide the antigenic basis for the development of improved diagnostic tests for the detection of PRRS virus antibodies.

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

Viruses ◽

10.3390/v11100880 ◽

2019 ◽

Vol 11 (10) ◽

pp. 880 ◽

Cited By ~ 4

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.

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Reactogenicity and Immunogenicity of the Pfizer and AstraZeneca COVID-19 Vaccines

Frontiers in Immunology ◽

10.3389/fimmu.2021.794642 ◽

2021 ◽

Vol 12 ◽

Author(s):

Waleed H. Mahallawi ◽

Walaa A. Mumena

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Weight Status ◽

Age Groups ◽

Vaccine Dose ◽

Cross Sectional Study ◽

Enzyme Linked Immunosorbent Assay ◽

Cross Sectional ◽

Humoral Immune ◽

Related Symptom

BackgroundThe relationships of the coronavirus disease 2019 (COVID-19) vaccination with reactogenicity and the humoral immune response are important to study. The current study aimed to assess the reactogenicity and immunogenicity of the Pfizer and AstraZeneca COVID-19 vaccines among adults in Madinah, Saudi Arabia.MethodsA cross-sectional study, including 365 randomly selected adult Pfizer or AstraZeneca vaccine recipients who received a homologous prime-boost vaccination between February 1st and June 30th, 2021. Data of height and weight were collected to assess the weight status of percipients. An evaluation of seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies was assessed using enzyme-linked immunosorbent assay (ELISA).ResultsAmong the participants, 69% (n = 250) reported at least one vaccine-related symptom. Pain at the injection site was the most frequently reported vaccine-related symptom. The mean total score for vaccine-related symptoms was significantly higher among participants who received the AstraZeneca vaccine, women, and participants with no previous COVID-19 infection (p < 0.05). Spike-specific IgG antibodies were detected in 98.9% of participants after the receipt of two vaccine doses, including 99.5% of Pfizer vaccine recipients and 98.3% of AstraZeneca vaccine recipients. Significantly, higher proportions of participants in the <35-year age group developed a humoral immune response after the first vaccine dose compared with the participants in other age groups.ConclusionParticipants who received the Pfizer COVID-19 vaccine reported fewer vaccine-related complications compared with those who received the AstraZeneca COVID-19 vaccine, but no serious side effects were reported in response to either vaccine. Health status and age were factors that may influence COVID-19 vaccine effectiveness for the generation of antibodies against the SARS-CoV-2 spike protein.

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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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Comprehensive antibody profiling of mRNA vaccination in children

10.1101/2021.10.07.463592 ◽

2021 ◽

Author(s):

Yannic C Bartsch ◽

Kerri J St Denis ◽

Paulina Kaplonek ◽

Jaewon Kang ◽

Evan C Lam ◽

...

Keyword(s):

Immune Response ◽

Young Children ◽

Receptor Binding ◽

Humoral Immune Response ◽

Antibody Responses ◽

Fcγ Receptor ◽

Humoral Immune ◽

Antibody Titers ◽

Antibody Profiling ◽

Vaccines For Children

With the emergence of SARS-CoV-2 variants, fluctuating mask mandates, and school re-openings, increased infections and disease surged among children recently. Thus, there is an urgent need for COVID-19 vaccines for children of all ages. However, whether young children will respond appropriately to mRNA vaccines remains unclear. Here, we deeply profiled the vaccine-induced humoral immune response in 7-11 year old children receiving the mRNA-1273 vaccine. Vaccinated children induced significantly higher antibody titers and functions compared to naturally infected children. Moreover, we observed comparable SARS-CoV-2 titers and neutralizing activity across variants of concern and superior Fcγ-receptor binding and phagocytic antibodies in children compared to vaccinated adults. Our data indicate that mRNA vaccination elicits robust antibody responses and drives superior antibody functionality in children.

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