scholarly journals Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

2004 ◽  
Vol 11 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Marli S. P. Azevedo ◽  
Lijuan Yuan ◽  
Cristiana Iosef ◽  
Kyeong-Ok Chang ◽  
Yunjeong Kim ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Vaccine Regimen ◽  
Rotavirus Vaccines ◽  
Antibody Titers ◽  
Iga Antibody ◽  
Gnotobiotic Pigs

ABSTRACT A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05) intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers postchallenge compared to those in the other groups. Statistical analyses of the correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers and protection demonstrated that each of these was an indicator of protective immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA and not IgM or IgG antibody titers in serum were highly correlated (R 2 = 0.89; P < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines among all the vaccinated groups, indicating that the IgA antibody titer is probably the most reliable indicator of protection.

scholarly journals Heterotypic Protection and Induction of a Broad Heterotypic Neutralization Response by Rotavirus-Like Particles

1999 ◽  
Vol 73 (6) ◽  
pp. 4813-4822 ◽  
Author(s):  
Sue E. Crawford ◽  
Mary K. Estes ◽  
Max Ciarlet ◽  
Christopher Barone ◽  
Christine M. O’Neal ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Diarrheal Disease ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Rotavirus Vaccines ◽  
Life Threatening ◽  
And Control ◽  
Potential Use ◽  
Neutralization Response

ABSTRACT The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11. Immunization with VLPs may provide sufficient priming of the immune system to induce protective anamnestic heterotypic neutralizing antibody responses upon subsequent rotavirus infection. Therefore, a limited number of serotypes of VLPs may be sufficient to provide a broadly protective subunit vaccine.

scholarly journals Emergency response for evaluating SARS-CoV-2 immune status, seroprevalence and convalescent plasma in Argentina

2021 ◽  
Vol 17 (1) ◽  
pp. e1009161 ◽  
Author(s):  
Diego S. Ojeda ◽  
María Mora Gonzalez Lopez Ledesma ◽  
Horacio M. Pallarés ◽  
Guadalupe S. Costa Navarro ◽  
Lautaro Sanchez ◽  
...  
Keyword(s):  
Longitudinal Studies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Health Authorities ◽  
New Information ◽  
Wide Range ◽  
Private And Public ◽  
Antibody Titers

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.

scholarly journals Generation of Female Genital Tract Antibody Responses by Local or Central (Common) Mucosal Immunization

2000 ◽  
Vol 68 (10) ◽  
pp. 5539-5545 ◽  
Author(s):  
Hong-Yin Wu ◽  
Samira Abdu ◽  
Dana Stinson ◽  
Michael W. Russell
Keyword(s):  
Genital Tract ◽  
Molecular Form ◽  
Female Genital Tract ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Igg Antibody ◽  
B Subunit ◽  
Iga Antibody ◽  
The Common ◽  
Female Genital

ABSTRACT Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin. Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses. Although i.vag. immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated. In contrast, i.n. immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva. Moreover, mucosal and systemic antibodies induced by i.n. immunization persisted for at least 12 months. Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.

scholarly journals The immune landscape of IgA induction in the gut

2021 ◽  
Author(s):  
Claudia Seikrit ◽  
Oliver Pabst
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Dark Side ◽  
Secretory Immunoglobulin A ◽  
Antibody Isotype ◽  
Mucosal Antibody ◽  
Key Concepts ◽  
Basic Understanding ◽  
Secretory Immunoglobulin

AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.

scholarly journals An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Martijn A. Langereis ◽  
Irina C. Albulescu ◽  
Judith Stammen-Vogelzangs ◽  
Morindy Lambregts ◽  
Ken Stachura ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Animal Species ◽  
Close Contact ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Replicon Particle ◽  
Nasal Swabs ◽  
Animal Hosts

AbstractEarly in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

scholarly journals Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 964
Author(s):  
Kelsey A. Pilewski ◽  
Kevin J. Kramer ◽  
Ivelin S. Georgiev
Keyword(s):  
Specific Antibody ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Emerging Pathogens ◽  
Igg Antibody ◽  
Neisseria Meningitides ◽  
Immunization Strategies ◽  
Single Antigen ◽  
The Face ◽  
Antibody Titers

Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.

scholarly journals Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients

2021 ◽  
Author(s):  
Jira Chansaenroj ◽  
Ritthideach Yorsaeng ◽  
Nasamon Wanlapakorn ◽  
Chintana Chirathaworn ◽  
Natthinee Sudhinaraset ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Immunological Study ◽  
Igg Antibody ◽  
Vaccine Schedule

Abstract Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 in a cohort of patients who were previously infected with SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of SARS-CoV-2 infection were enrolled in our immunological study. The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5 – 327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time depends on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

scholarly journals Immunoglobulin A Antibody Responses in Dengue Patients: a Useful Marker for Serodiagnosis of Dengue Virus Infection

2005 ◽  
Vol 12 (10) ◽  
pp. 1235-1237 ◽  
Author(s):  
M. Nawa ◽  
T. Takasaki ◽  
M. Ito ◽  
S. Inoue ◽  
K. Morita ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Infections ◽  
Serum Samples ◽  
Dengue Virus Infection ◽  
Iga Antibody ◽  
Antibody Capture

ABSTRACT We determined the usefulness of an immunoglobulin A (IgA) antibody-capture enzyme-linked immunosorbent assay for serodiagnosis of dengue virus infections. The results indicate that the presence of IgA and IgM in serum samples assures recent primary dengue virus infection even with a single serum sample.

ANTIBODY RESPONSES TO NATURALLY OCCURRING POLIOMYELITIS INFECTIONS

PEDIATRICS ◽  
1956 ◽  
Vol 17 (4) ◽  
pp. 489-502
Author(s):  
C. Arden Miller ◽  
Margaret F. Lenahan
Keyword(s):  
Diagnostic Tool ◽  
Test Procedure ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Paralytic Poliomyelitis ◽  
Repeat Testing ◽  
Household Contacts ◽  
Naturally Occurring ◽  
Antibody Titers ◽  
Fecal Virus

The neutralizing antibody responses of 52 asymptomatic household contacts of patients with poliomyelitis were studied by the metabolic inhibition method. Half of these contacts were fecal carriers of poliomyelitis virus. For purposes of comparison the antibody responses of 25 patients with paralytic poliomyelitis, all fecal virus carriers, were studied. The errors of replication of the test procedure were determined by duplicate testing of 51 serums. Duplicate testing of serum specimens indicated disagreement regarding the presence or absence of antibody in 6.0 to 8.0 per cent of the serums. The second test gave antibody titers which disagreed with those from the first test by a factor of fourfold or more 37.0 per cent of the time; errors occurred equally in either direction. Half of all persons studied showed an increase of fourfold or more in the antibody titers of paired serums; this was 3 to 4 times as many as would be expected by chance. It was not possible to distinguish the antibody responses of paralyzed patients from asymptomatic household contacts; or the fecal virus carriers from the nonvirus carriers in the latter group. Four virus carriers who did not have homologous antibody in convalescent serums were found. By repeat testing homologous antibody was found in all but one of these. The limitations of the test procedure as a diagnostic tool are discussed.

scholarly journals Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 989
Author(s):  
Hae-Ji Kang ◽  
Ki-Back Chu ◽  
Min-Ju Kim ◽  
Hyunwoo Park ◽  
Hui Jin ◽  
...  
Keyword(s):  
B Cells ◽  
Toxoplasma Gondii ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Strongly Correlated ◽  
Cpg Odn ◽  
Virus Like Particle ◽  
Iga Antibody ◽  
Specific Igg

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

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