scholarly journals Immunogenicity of BNT162b2 and CoronaVac boosters in fully vaccinated individuals with CoronaVac against SARS-CoV-2: A Longitudinal Study

Author(s):  
Füsun Can ◽  
Zeynep Ece Kuloğlu ◽  
Rojbin El ◽  
Gülen Esken ◽  
Yeşim Tok ◽  
...  

Objective: There is a need for the immunogenicity of different boosters after widely used inactivated vaccine regimens. We aimed to determine the effects of BNT162b2 and CoronaVac boosters on the humoral and cellular immunity of individuals who had two doses of CoronaVac vaccination. Methods: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul. Individuals who had two doses of CoronaVac and no history of COVID-19 were included. The baseline blood samples were collected three to five months after two doses of CoronaVac. Follow-up samples were taken one and three months after third doses of CoronaVac or one dose of mRNA BNT162b2 boosters. Neutralizing antibody titers were detected by plaque reduction assay. T cell responses were evaluated by Elispot assay and flow cytometry. Results: We found a 3.38-fold increase in neutralizing antibody titers (Geometric Mean Titer [GMT], 78.69) one month after BNT162b2 booster and maintained at the three months (GMT, 80). However, in the CoronaVac group, significantly lower GMTs than BNT162b2 after 1 month and 3 months (21.44 and 28.44, respectively) indicated the weak immunogenicity of the CoronaVac booster (p<0.001). In the ELISpot assay, IL-2 levels after BNT162b2 were higher than baseline and CoronaVac booster (p<0.001) and IFN-γ levels were significantly higher than baseline (P<0.001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated significantly at the 3 month of the BNT162b2 boosters. Conclusion: The neutralizing antibody levels after three months of the BNT162b2 booster were higher than the antibody levels after CoronaVac. On the other hand, specific T cells might contribute to immune protection. By considering the waning immunity, we suggest a new booster dose with BNT162b2 for the countries that already have two doses of primary CoronaVac regimens.

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1027
Author(s):  
Nima Taefehshokr ◽  
Sina Taefehshokr ◽  
Bryan Heit

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.


Author(s):  
Andrea Padoan ◽  
Chiara Cosma ◽  
Francesco Bonfante ◽  
Foscarina della Rocca ◽  
Francesco Barbaro ◽  
...  

Abstract Objectives mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. Methods A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). Results The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1–92.8%) for S-RBD IgG, 82% (58.6–89.3%) for trimeric-S, 70.4% (34.5–86.4%) for VNT-Nab, 75% (50–87.5%) for PRNT50 and 75% (50–93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). Conclusions After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.


2021 ◽  
Author(s):  
Harmony L. Tyner ◽  
Mark G. Thompson ◽  
Jefferey L. Burgess ◽  
Lauren Grant ◽  
Manjusha Gaglani ◽  
...  

Background: Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited. Methods: From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models. Results: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose-2. Conclusions: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS-CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.


2021 ◽  
Author(s):  
Hideaki Kato ◽  
Kei Miyakawa ◽  
Norihisa Ohtake ◽  
Yutaro Yamaoka ◽  
Satoshi Yajima ◽  
...  

To evaluate vaccine-induced humoral and cell-mediated immunity at 6 months post BNT162b2 vaccination, immunoglobulin G against SARS-CoV-2 spike protein (SP IgG), 50% neutralizing antibody (NT50), and spot-forming cell (SFC) counts were evaluated by interferon-γ releasing ELISpot assay of 98 healthy subjects (median age, 43 years). The geometric mean titers of SP IgG and NT50 decreased from 95.2 (95% confidence interval (CI) 79.8-113.4) to 5.7 (95% CI 4.9-6.7) and from 680.4 (588.0-787.2) to 130.4 (95% CI 104.2-163.1), respectively, at 3 weeks and 6 months after the vaccination. SP IgG titer was negatively correlated with age and alcohol consumption. Spot-forming cell counts at 6 months did not correlate with age, gender, and other parameters of the patients. SP IgG, NT50, and SFC titers were elevated in the breakthrough infected subjects. Although the levels of vaccine-induced antibodies dramatically declined at 6 months after vaccination, a certain degree of cellular immunity was observed irrespective of the age.


2014 ◽  
Vol 1 (3) ◽  
Author(s):  
Amy Parker Fiebelkorn ◽  
Laura A. Coleman ◽  
Edward A. Belongia ◽  
Sandra K. Freeman ◽  
Daphne York ◽  
...  

Abstract Background.  Mumps outbreaks in populations with high 2-dose measles-mumps-rubella (MMR) vaccine coverage raise the question whether a third dose of MMR vaccine (MMR3) is needed. However, data on the immunogenicity of MMR3 are limited. We assessed mumps virus neutralizing antibody levels pre- and post-MMR3 in a nonoutbreak setting. Methods.  Mumps antibody titers were assessed at baseline, 1 month, and 1 year after MMR3 in subjects aged 18–28 years. Results.  At baseline, 5 of 656 (0.8%) subjects had seronegative mumps neutralizing antibody titers and 38 (5.8%) had low titers. One year post-MMR3, these numbers declined to 3 (0.5%) and 16 (2.4%), respectively. Subjects with low baseline titers were more likely to have low 1-month and 1-year titers (R2 = 0.81–0.87, P &lt; .0001). Compared to baseline, geometric mean titers were significantly higher at 1 month (P &lt; .0001) and 1 year (P &lt; .01) post-MMR3; however, reverse cumulative distribution curves showed only minimal shifts in mumps titers from baseline to 1 month and 1 year. Conclusions.  Very few subjects had negative or low baseline mumps titers. Nonetheless, mumps titers had modest but significant increases when measured 1 month and 1 year post-MMR3. This temporary increase in titers could decrease susceptibility to disease during outbreaks, but may have limited value for routine use in vaccinated populations.


2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.


2019 ◽  
Vol 31 (4) ◽  
pp. 288-295 ◽  
Author(s):  
Adrienne Guignard ◽  
François Haguinet ◽  
Stéphanie Wéry ◽  
Phirangkul Kerdpanich

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.


2020 ◽  
Vol 12 (564) ◽  
pp. eabd5487 ◽  
Author(s):  
Carl A. Pierce ◽  
Paula Preston-Hurlburt ◽  
Yile Dai ◽  
Clare Burn Aschner ◽  
Natalia Cheshenko ◽  
...  

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor–α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.


2020 ◽  
Vol 223 (1) ◽  
pp. 47-55 ◽  
Author(s):  
William T Lee ◽  
Roxanne C Girardin ◽  
Alan P Dupuis ◽  
Karen E Kulas ◽  
Anne F Payne ◽  
...  

Abstract Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (&gt;960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4685-4685
Author(s):  
Piotr Centkowski ◽  
Lidia Brydak ◽  
Magdalena Machala ◽  
Ewa Kalinka ◽  
Maria Blasinska-Morawiec ◽  
...  

Abstract We assessed humoral response to influenza vaccination (vacc) in two consecutive seasons 2003/2004 and 2004/2005 in 123 NHL patients. In season 03/04 50 patients (29 previously treated with chemotherapy - group A03/04 and 21 not treated - group B03/04) and 73 patients in season 04/05: 34 treated - A04/05, 39 not treated - B04/05 were vaccinated with trivalent subunit influenza vaccine. Antibody responses to influenza hemagglutinin (HI) and neuraminidase (NI) were determined in sera collected before vacc, after 1 month and after 6 months. One month after vacc geometric mean antibody titers (GMTs) of antiHI antibodies significantly increased (p<0.05) and mean fold increases (MFIs) ranged from 10.4 to 24.3 in A03/04, 10.9–11.7 in A04/05, 6.5–31.6 in B03/04 and 14.8–21 in B04/05, than fell after 6 months to 3.6–7.8 in A03/04, 3.7–4.4 in A04/05, 1.7–11.2 in B03/04 and 7.8–8.5 in B04/05. Prevacc protection rate, i.e. the number of subjects with the protective HI antibody titers >1:40, ranged from 3.4 to 10.3% in A03/04, 2.9-8.8% in A04/05, 0–4.6% in B03/04 and 0–5.1% in B04/05. After 1 month protection rates ranged from 78.1 to 87.5% in A03/04, 61.8–70.6% in A04/05, 73.3–93.3% in B03/04 and 66.7–74.4% in B04/05 and decreased after 6 months to 24.1–37.9% in A03/04, 32.4–35.3% in A04/05, 19–47.6% in B03/04 and 17.9–35.9% in B04/05. Response rates, i.e. the number of subjects with at least a 4-fold increase of antiHI antibody titers after vacc, ranged from 58.6–75.9% in A03/04, 50–67.6% in A04/05, 57.1–81% in B03/04 and 61.5–71.8% in B04/05. Six months after vacc it decreased to 17.2–34.5% in A03/04, 20.6–29.4% in A04/05, 19–38.1% in B03/04 and 15.4–33.3% in B04/05. In all patients’ groups, post-vacc antiNI GMTs were significantly higher (p<0.05) than pre-vacc. MFIs of antiNI antibodies 1 month after vacc ranged from 11 to 17.5 in A03/04, 4.1–9.4 in A04/05, 5.1–9.9 in B03/04 and 6.3–9.9 in B04/05, then fell to 2.9–6.9 in A03/04, 1.3–5.1 in A04/05, 3.4–4.9 in B03/04 and 2.8–3.6 in B04/05. In season 03/04 only hemagglutinin H1 antibody titers were significantly higher in CTR than in patients in contrast of season 04/05 when in patients the titers of H1, H3 and N1, N2, NB were significantly lower. We conclude that the response to influenza vaccine is similar in patients previously treated and not-treated with chemoterapy. It is highly immunogenic in NHL patients, but the level of specific antibodies is variable and may depend on immunogenecity of vaccine for actual season. After 6 months the antibody titers rapidly decline, thus the NHL patients may need the second dose of vaccine to maintain good protective level.


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