scholarly journals A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

Author(s):  
Barbara M Schultz ◽  
Felipe Melo-Gonzalez ◽  
Luisa F Duarte ◽  
Nicolas MS Galvez ◽  
Gaspar A Pacheco ◽  
...  

Numerous vaccines have been generated to decrease the morbidity and mortality of COVID-19. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO) to prevent COVID-19 that has safety and immunogenicity profiles described in different clinical trials. We previously reported an increase in levels of neutralizing antibodies two- and four-weeks after administering two doses of CoronaVac® in a two-week interval (0-14 day) vaccination schedule, as compared to pre-immune sera in adults in the Chilean population that are participating in phase 3 clinical trial. Here we report the levels of antibodies directed against the Receptor Binding Domain of the SARS-CoV-2 spike protein comparing their neutralizing capacities and the cellular response at five months after the second dose and four weeks after a booster (third) dose in volunteers immunized with two doses of CoronaVac®in a four-week interval (0-28 day) vaccination schedule. We observed a decrease in the levels of anti-SARS-CoV-2 antibodies with neutralizing capacities five months after the second dose (GMU 39.0 95% confidence interval (CI)(32.4-47.0), which increased up to 12 times at four weeks after the booster dose (GMU 499.4, 95% CI=370.6-673.0). Equivalent results were observed in adults aged 18-59 years old and individuals ≥60 years old. In the case of cellular response, we observed that activation of specific CD4+ T cells increases in time and reaches its maximum at four weeks after the booster dose in both groups. Our results support the notion that a booster dose of the SARS-CoV-2 inactivated vaccine increases the levels of neutralizing antibodies and the specific cellular response in adults of both groups, which is likely to boost the protective capacity of these vaccines against COVID-19.

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1346
Author(s):  
Priya Veluswamy ◽  
Max Wacker ◽  
Dimitrios Stavridis ◽  
Thomas Reichel ◽  
Hendrik Schmidt ◽  
...  

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.


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.


Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 355
Author(s):  
Sebastian Elgueta ◽  
Marcela Valenzuela ◽  
Marcela Fuentes ◽  
Pablo Meza ◽  
Juan Pablo Manzur ◽  
...  

Over the last years, the detection of pesticide residues in the official food surveillance programs of Chile has been increased, mainly in fresh vegetables such as tomatoes and lettuces. The Metropolitana Region of Chile presents the highest detections in the country. The lack of evaluations of toxicological risks in human health have increased uncertainty of the potential effects of pesticides exposures in the Chilean population. This research aims to determinate health risks assessment of pesticide residues associated to tomatoes and lettuces produced in Metropolitana Region. The findings of this study reveal that tomatoes and lettuces cultivated in the MR show more than 50% of samples with one or multiple pesticides residues. From the total samples, 16% were over the Chilean Maximum Residue Levels (MRLs). The main pesticides detected in tomatoes and lettuces were methamidophos, methomyl, difenoconazole, cyprodinil and boscalid. The results obtained using the official data of the Ministry of Health of Chile (MINSAL) compared to the World Health Organization (WHO), describe relevant risks through the Estimated Daily Intakes (EDI), Hazard Quotients (HQ) and Hazard Index (HI) for the Chilean population due to high concentrations of methamidophos, methomyl and cyprodinil. More restrictions for the use of methamidophos, methomyl, difenoconazole, cyprodinil and boscalid and effective control programs should be implemented in order to mitigate the impacts on the Chilean population.


2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.


Author(s):  
Yihao Liu ◽  
Qin Zeng ◽  
Caiguanxi Deng ◽  
Mengyuan Li ◽  
Liubing Li ◽  
...  

AbstractSARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccine and the potential need for a third booster dose for the HCWs. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 31.2 AU/ml to 9.2 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 66.8 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly “no responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which has implications for future booster strategies that the frontline HCWs, individuals with low serological response to 2 dose of vaccine and immune compromised patients could benefit from a third dose of inactivated vaccine.


1969 ◽  
Vol 67 (4) ◽  
pp. 609-618 ◽  
Author(s):  
A. W. Downie ◽  
L. St Vincent ◽  
L. Goldstein ◽  
A. R. Rao ◽  
C. H. Kempe

SUMMARYTwo hundred and sixteen sera from 151 patients suffering from smallpox (non-haemorrhagic) were examined for antibody by precipitation in agar gel, by haemagglutinin inhibition (HI), complement fixation (CF) and neutralization tests. Most of the patients were adults and the majority had been vaccinated earlier in life. HI and neutralizing antibodies showed rising titres from the 6th day of illness while the majority showed precipitins and CF antibodies from the 8th day. The results of the precipitation-in-agar-gel tests are in marked contrast to the findings in healthy vaccinated and revaccinated individuals, none of whose sera gave a positive result for antibody by this technique. In unvaccinated patients the antibody response was frequently delayed and the titres lower than those attained by the previously vaccinated patients. There was no exact correlation in antibody titres obtained by the four methods of measurement, HI antibody, in particular, reaching in some cases relatively high titres when other tests showed low titres. It is suggested that with the methods and materials used, a positive precipitation test in agar gel, a CF titre of 1/20 or more and an HI titre of 1/80 or higher in a single specimen of serum would be suggestive of recent smallpox infections. Such a result might be of special value in the retrospective diagnosis of missed cases and in the detection of minimal or subclinical infections.This investigation was supported in part by Public Health Service Grant AI–1632–16 VR from the National Institute of Allergy and Infectious Diseases, by the World Health Organization and by the Marcus T. Reynolds III Fund.


2021 ◽  
Author(s):  
Amit Kumar ◽  
Elena E Giorgi ◽  
Joshua J Tu ◽  
David R Martinez ◽  
Joshua Eudailey ◽  
...  

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p=0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy could drive the evolution of variants fit for vertical transmission.


Author(s):  
Insuk Sim ◽  
Yun-Jung Kang

The coronavirus disease (COVID-19) pandemic, which began in December 2019, spread rapidly across Asian countries in January and February 2020 and again after March 2020. COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by fever, cough, and dyspnea. On January 31, 2020, the World Health Organization declared the Public Health Emergency of International Concern. Quarantine authorities are constantly working to prevent the spread of COVID-19. One of the control measures is preparing for national antibody testing, as another wave of infection is expected to occur in the fall of 2021. There are three reasons for antibody testing from a prevention perspective. First, it can identify people with asymptomatic infection. Second, it can detect whether neutralizing antibodies are produced in individuals who have already been infected. Third, it can confirm collective immunity at a community or population level. Considering the lack of effective antiviral drugs or vaccines, the strategy of implementing an effective antibody testing program is an important control measure to minimize the damage caused by the COVID-19 pandemic.


2021 ◽  
Vol 12 (5) ◽  
pp. 6895-6914

COVID-19 is caused by the virus SARS-CoV-2 that belongs to the Corona groups. The subgroups of the coronavirus families are α, β, γ, and δ coronavirus. On June 15, 2021, the string λ of SARS-CoV-2 was evaluated as a variant of interest via the World Health Organization. This string has a high prevalence in some parts of South American countries, but it occurred only occasionally in Brazil. This study confirms that mutations in the λ -spike protein can be destroyed the neutralizing antibodies and increase infectivity. Coronaviruses such as SARS-CoV-2 have an evolutionary superpower called “recombination” which permits the mixing of their genomes into novel combinations. Unlike regular mutation, which precedes slowly one change at a time, recombination can produce whole changes in a coronavirus genome. Although right now, δ-variant is a concern, a mixing of λ with other variants such as δ-variant is much more of a concern compared to alone variants. There is another item: the recombination can arise within the sample after it was taken from the infected person, not while it was inside their body.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Supangat ◽  
Elly Nurus Sakinah ◽  
Muhammad Yuda Nugraha ◽  
Tegar Syaiful Qodar ◽  
Bagus Wahyu Mulyono ◽  
...  

Abstract Introduction Coronavirus Disease (COVID-19) caused by Novel Coronavirus named as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was declared Pandemic by The World Health Organization (WHO) and a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. Many COVID-19 vaccines have been developed, including CoronaVac vaccines by Sinovac. Health care workers, along with medical clerkship students are the priority to receive the vaccine. However, the Adverse Events Following Immunization (AEFI) of the CoronaVac remains unclear. This study aims to describe and analyze the adverse events following immunization (AEFI) of COVID-19 vaccination in medical students in clerkship programs. Method We conducted a cross-sectional study using a questionnaire to assess AEFI after CoronaVac vaccination among medical clerkship students. A Chi-Square test with 95 % of CI was used to determine whether gender correlated with symptoms of AEFI. Result We identified 144 medical clerkship students. The most common AEFI of SARS-CoV-2 vaccinations was localized pain in the injection site during the first dose with 25 (45 %) reports and the booster dose with 34 (67 %) reports. Then followed by malaise, the first dose with 20 (36 %) reports and the booster dose with 21 (41 %) reports. Other symptoms like headache, fever, shivering, sleepiness, nausea, dysphagia, and cold were also reported. Conclusions CoronaVac SARS-COV-2 vaccine has several mild symptoms of AEFI and not correlated with gender. Nevertheless, follow-up after vaccination is needed to prevent immunologic responses that may occur in some patients.


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