VACCINATION-RELATED CLINICAL PARAMETERS AND VIRUS-NEUTRALIZATION LEVEL AFTER SMALLPOX REVACCINATION

Mass vaccination with vaccinia virus resulted in smallpox eradication, that was later cancelled due to potential of developing severe complications. Reappraisal of scientific interest to smallpox vaccine was accounted for by emerged threat of using relevant virus as a bioweapon as well as increased frequency of orthopoxvirus infections paralleled with decline in population immunity. The vaccinia virus is also used as a vector for generating recombinant vaccines. Understanding mechanisms behind formation of immune response and opportunity for forecasting its modality may allow to avoid potential adverse events and excessive immunization.The aim of the study was to assess a link between humoral immunity, clinical signs related to vaccination period, adult sex and age characteristics in subjects received several doses of vaccinia virus. We examined vaccination-coupled clinical data obtained from 135 subjects revaccinated with a smallpox vaccine for 2-10 times. It was found that 95% and 5% vaccine recipients experienced mild or moderate vaccination-related signs, respectively.Inoculation skin lesions were observed in 127 subjects (94.1%), whereas 22% vaccine recipients experienced local and systemic adverse events. Mild vs. moderate vaccine signs group manifested greater hyperemia (p=0.04), scabbing (p=0.01), and duration of healing time (p=0.001). Younger subjects (p=0.03) and more frequent axillary adenopathy (p<0.001) were observed in moderate vs. mild vaccination period were at lower rate (p = 0.03), lymphadenopathy developed more often during moderate vaccination period (p<0.001).Vaccinia virus-neutralizing antibody titers were measured in 54 subjects by using plaque reduction neutralization tests. It was noted that protective antibody level tended to rise in females vs. males. A negative correlation between antibody titers and hyperemia degree was observed. Frequent axillary adenopathy was associated with higher serum protective antibody level. Vaccinia-virus neutralizing antibody titers were not associated with presence and size of inoculation lesion, elimination of skin crusts, age and previous vaccination records. The clinical variability and immune response after applying this vaccine by similar vaccination protocol would be accounted for by individual genetic differences remains to be further explored.

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Vaccination against Canine Distemper Virus Infection in Infant Ferrets with and without Maternal Antibody Protection, Using Recombinant Attenuated Poxvirus Vaccines

Journal of Virology ◽

10.1128/jvi.74.14.6358-6367.2000 ◽

2000 ◽

Vol 74 (14) ◽

pp. 6358-6367 ◽

Cited By ~ 46

Author(s):

Janet Welter ◽

Jill Taylor ◽

James Tartaglia ◽

Enzo Paoletti ◽

Charles B. Stephensen

Keyword(s):

Canine Distemper Virus ◽

Clinical Signs ◽

Neutralizing Antibody ◽

Maternal Antibody ◽

Canine Distemper ◽

Parenteral Immunization ◽

Multiple Routes ◽

Antibody Titers ◽

Group 3 ◽

Rabies Glycoprotein

ABSTRACT Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59;n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8,P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0.25) than did i.n. immunization with NYVAC-HF (0.88 ± 0.36; n = 9) and ALVAC-HF (0.61 ± 0.43; n = 9, P = 3 × 10−7), and survival was also significantly better in the i.n.-parenteral group (3 of 9) than in the other HF-vaccinated animals (none of 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple routes were not tested with the ALVAC vaccine. The results suggest that infant ferrets are less responsive to i.n. vaccination than are older ferrets and raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.

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Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

10.1101/2021.12.25.21268336 ◽

2021 ◽

Author(s):

Noa Eliakim Raz ◽

Amos Stemmer ◽

Yaara Leibovici-Weissman ◽

Asaf Ness ◽

Muhammad Awwad ◽

...

Keyword(s):

Adverse Events ◽

Neutralizing Antibodies ◽

Multivariable Analysis ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Clinical Frailty Scale ◽

Younger Adults ◽

The Third ◽

Antibody Titers ◽

Level 2

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.

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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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Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2

Pathogens ◽

10.3390/pathogens9121027 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1027

Author(s):

Nima Taefehshokr ◽

Sina Taefehshokr ◽

Bryan Heit

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Cell Function ◽

Adaptive Immune Response ◽

Neutralizing Antibody ◽

Humoral And Cellular Immunity ◽

Cell Responses ◽

Adaptive Immune ◽

Antibody Titers

The current coronavirus disease 2019 (COVID-19) pandemic, a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was first identified in December 2019 in China, and has led to thousands of mortalities globally each day. While the innate immune response serves as the first line of defense, viral clearance requires activation of adaptive immunity, which employs B and T cells to provide sanitizing immunity. SARS-CoV-2 has a potent arsenal of mechanisms used to counter this adaptive immune response through processes, such as T cells depletion and T cell exhaustion. These phenomena are most often observed in severe SARS-CoV-2 patients, pointing towards a link between T cell function and disease severity. Moreover, neutralizing antibody titers and memory B cell responses may be short lived in many SARS-CoV-2 patients, potentially exposing these patients to re-infection. In this review, we discuss our current understanding of B and T cells immune responses and activity in SARS-CoV-2 pathogenesis.

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Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay

Clinical and Vaccine Immunology ◽

10.1128/cvi.00109-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1105-1112 ◽

Cited By ~ 18

Author(s):

Richard Kennedy ◽

V. Shane Pankratz ◽

Eric Swanson ◽

David Watson ◽

Hana Golding ◽

...

Keyword(s):

Immune Responses ◽

Vaccinia Virus ◽

High Throughput ◽

Large Scale ◽

Statistical Approach ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Virus Neutralization Assay ◽

Antibody Titers ◽

High Throughput Assay

ABSTRACT Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.

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A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2

10.1101/2021.09.23.21262329 ◽

2021 ◽

Author(s):

Etienne Brochot ◽

Vianney Souplet ◽

Pauline Follet ◽

Pauline Ponthieu ◽

Christophe Olivier ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibody ◽

Viral Epitope ◽

Time Period ◽

Versatile Tool ◽

Comprehensive Picture ◽

Long Time ◽

Antibody Titers ◽

Combined Detection

Background: In the fight against SARS-COV-2, the development of serological assays based on different antigenic domains represent a versatile tool to get a comprehensive picture of the immune response or differentiate infection from vaccination beyond simple diagnosis. Objectives: Here we use a combination of the Nucleoprotein (NP), the Spike 1 (S1) and Spike 2 (S2) subunits, and the receptor binding domain (RBD) and N-terminal domain (NTD) of the Spike antigens from the Syrius-CoViDiag multiplex IgG assay, to follow the immune response to SARS-CoV-2 infection over a long time period and depending on disease severity. Results: Using a panel of 209 sera collected from 61 patients up to eight months after infection, we observed that most patients develop an immune response against multiple viral epitope, but anti-S2 antibodies seemed to last longer. For all the tested IgGs, we have found higher titers for hospitalized patients than for non-hospitalized ones. Moreover the combination of the five different IgG titers increased the correlation to the neutralizing antibody titers than if considered individually. Conclusion: Multiplex immunoassays have the potential to improve diagnostic performances, especially for ancient infection or mild form of the disease presenting weaker antibody titers. Also the combined detection of anti-NP and anti-Spike-derived domains can be useful to differentiate vaccination from viral infection and accurately assess the antibody potential to neutralize the virus.

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Redundancy and Plasticity of Neutralizing Antibody Responses Are Cornerstone Attributes of the Human Immune Response to the Smallpox Vaccine

Journal of Virology ◽

10.1128/jvi.02244-07 ◽

2008 ◽

Vol 82 (7) ◽

pp. 3751-3768 ◽

Cited By ~ 61

Author(s):

Mohammed Rafii-El-Idrissi Benhnia ◽

Megan M. McCausland ◽

Hua-Poo Su ◽

Kavita Singh ◽

Julia Hoffmann ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Safety Net ◽

Antibody Responses ◽

Smallpox Vaccine ◽

Human Antibody ◽

Neutralization Activity ◽

Antibody Titers ◽

Human Immune Response ◽

Human Immune

ABSTRACT The smallpox vaccine is widely considered the gold standard for human vaccines, yet the key antibody targets in humans remain unclear. We endeavored to identify a stereotypic, dominant, mature virion (MV) neutralizing antibody target in humans which could be used as a diagnostic serological marker of protective humoral immunity induced by the smallpox vaccine (vaccinia virus [VACV]). We have instead found that diversity is a defining characteristic of the human antibody response to the smallpox vaccine. We show that H3 is the most immunodominant VACV neutralizing antibody target, as determined by correlation analysis of immunoglobulin G (IgG) specificities to MV neutralizing antibody titers. It was determined that purified human anti-H3 IgG is sufficient for neutralization of VACV; however, depletion or blockade of anti-H3 antibodies revealed no significant reduction in neutralization activity, showing anti-H3 IgG is not required in vaccinated humans (or mice) for neutralization of MV. Comparable results were obtained for human (and mouse) anti-L1 IgG and even for anti-H3 and anti-L1 IgG in combination. In addition to H3 and L1, human antibody responses to D8, A27, D13, and A14 exhibited statistically significant correlations with virus neutralization. Altogether, these data indicate the smallpox vaccine succeeds in generating strong neutralizing antibody responses not by eliciting a stereotypic response to a single key antigen but instead by driving development of neutralizing antibodies to multiple viral proteins, resulting in a “safety net” of highly redundant neutralizing antibody responses, the specificities of which can vary from individual to individual. We propose that this is a fundamental attribute of the smallpox vaccine.

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Microneedle-Based Intradermal Delivery of the Anthrax Recombinant Protective Antigen Vaccine

Infection and Immunity ◽

10.1128/iai.01210-06 ◽

2006 ◽

Vol 74 (12) ◽

pp. 6806-6810 ◽

Cited By ~ 84

Author(s):

John A. Mikszta ◽

John P. Dekker ◽

Noel G. Harvey ◽

Cheryl H. Dean ◽

John M. Brittingham ◽

...

Keyword(s):

Immune Response ◽

Immunoglobulin G ◽

Protective Antigen ◽

Neutralizing Antibody ◽

Antigen Vaccine ◽

Intradermal Delivery ◽

Antibody Titers ◽

Sparing Effect ◽

Booster Inoculation ◽

Recombinant Protective Antigen

ABSTRACT The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 μg of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.

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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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Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain

10.21203/rs.3.rs-77625/v1 ◽

2020 ◽

Author(s):

Emmanuelle Billon-Denis ◽

Audrey Ferrier-Rembert ◽

Annabelle Garnier ◽

Laurence Cheutin ◽

Clarisse Vigne ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Binding Domain ◽

Clinical Severity ◽

Individual Factors ◽

Receptor Binding Domain ◽

Antibody Titers ◽

Antibody Dynamics

Abstract BackgroundWe report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CaseOne patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. Discussion and ConclusionThus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

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