scholarly journals Long-lasting cellular immunity to SARS-CoV-2 following infection or vaccination and implications for booster strategies

2021 ◽  
Author(s):  
Alessio Mazzoni ◽  
Anna Vanni ◽  
Michele Spinicci ◽  
Giulia Lamacchia ◽  
Seble Tekle Kiros ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Booster Dose ◽  
Natural Infection ◽  
Severe Disease ◽  
Immunological Memory ◽  
Short Term ◽  
Humoral And Cellular Immunity ◽  
One Year ◽  
Antibody Levels ◽  
Kinetics Of

AbstractImmunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last. We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 following mRNA vaccination in naïve and COVID-19 recovered individuals. We found that cellular immunity is still detectable 8 months after vaccination, while antibody levels decline significantly especially in naïve subjects. We also found that a booster injection is more efficacious in reactivating immunological memory to spike protein in naïve than in previously SARS-CoV-2 infected subjects. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to one year following natural infection in a cohort of unvaccinated individuals. Short-term persistence of humoral immunity may account for reinfections and breakthrough infections, although long-lived memory B and CD4+ T cells may protect from severe disease. A booster dose restores optimal anti-spike immunity in naïve subjects, while the need for vaccinated COVID-19 recovered subjects has yet to be defined.

scholarly journals Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
One Year ◽  
Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

scholarly journals SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 in the UK general population

2021 ◽  
Author(s):  
Jia Wei ◽  
Koen B. Pouwels ◽  
Nicole Stoesser ◽  
Philippa C. Matthews ◽  
Ian Diamond ◽  
...  
Keyword(s):  
General Population ◽  
Booster Dose ◽  
Peak Level ◽  
Antibody Responses ◽  
Short Term ◽  
Igg Antibody ◽  
The Uk ◽  
Dosing Intervals ◽  
Antibody Levels ◽  
Prior Infection

We investigated anti-spike IgG antibody responses following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 186,527 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Antibody levels declined faster at older ages than younger ages with BNT162b2, but were similar across ages with ChAdOX1. With both vaccines, prior infection significantly increased antibody peak level and half-life. Protection was estimated to last for 0.5-1 year after ChAdOx1 and >1 year after BNT162b2, but could be reduced against emerging variants. Reducing the dosing interval to 8 weeks for both vaccines or further to 3 weeks for BNT162b2 may help increase short-term protection against the Delta variant. A third booster dose may be needed, prioritised to more vulnerable people.

scholarly journals A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

2015 ◽  
Vol 90 (5) ◽  
pp. 2551-2560 ◽  
Author(s):  
Rekha Dhanwani ◽  
Yanqin Zhou ◽  
Qinfeng Huang ◽  
Vikram Verma ◽  
Mythili Dileepan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Booster Dose ◽  
Vaccination Strategy ◽  
Vaccine Vector ◽  
Humoral And Cellular Immunity ◽  
Pichinde Virus ◽  
Boost Vaccination ◽  
Foreign Genes

ABSTRACTPichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growthin vitroand expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a prime-and-boost vaccination strategy.IMPORTANCEWe have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this live rP18tri vector to be used as a novel vaccine platform for a prime-and-boost vaccination strategy.

scholarly journals The longitudinal kinetics of antibodies in COVID-19 recovered patients over 14 months

2021 ◽  
Author(s):  
Tsuf Eyran ◽  
Anna Vaisman-Mentesh ◽  
Yeal Dror ◽  
Ligal Aizik ◽  
Aya Kigel ◽  
...  
Keyword(s):  
Decision Making ◽  
Decay Rate ◽  
Natural Infection ◽  
Serological Response ◽  
Specific Antibodies ◽  
Antibody Levels ◽  
Antibody Kinetics ◽  
Kinetics Of

Here, we describe the longitudinal kinetics of the serological response in COVID-19 recovered patients over the period of 14 months. The antibody kinetics in a cohort of 200 recovered patients with 89 follow up samples at 2-4 visits reveal that RBD-specific antibodies decay over the period of 14 month following the onset of symptoms. The decay rate is associated with the robustness of the response thus, recovered patients that exhibit elevated antibody levels at the first visit, experience faster decay. We further explored the longitudinal kinetics differences between recovered patients and naive BNT162b2 vaccinees. We found a significantly faster decay in naive vaccinees compared to recovered patients suggesting that the serological memory following natural infection is more robust compared to vaccination. Our data highlights the differences between serological memory induced by natural infection vs. vaccination, facilitating the decision making in Israel regarding the 3rd dose vaccination.

scholarly journals One-year timeline kinetics of cytokine-mediated cellular immunity in dogs vaccinated against visceral leishmaniasis

2015 ◽  
Vol 11 (1) ◽  
Author(s):  
Christiane Costa-Pereira ◽  
Marcela L Moreira ◽  
Rodrigo P Soares ◽  
Bruno H Marteleto ◽  
Vitor M Ribeiro ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Cellular Immunity ◽  
One Year ◽  
Kinetics Of

scholarly journals Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression

2009 ◽  
Vol 15 (19) ◽  
pp. 6113-6127 ◽  
Author(s):  
A.K.M. Ghulam Muhammad ◽  
Marianela Candolfi ◽  
Gwendalyn D. King ◽  
Kader Yagiz ◽  
David Foulad ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cellular Immunity ◽  
Tumor Regression ◽  
Immunological Memory ◽  
Humoral And Cellular Immunity

scholarly journals Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 patients reveal immune persistence up to 9 months after infection

2021 ◽  
Author(s):  
John Tyler Sandberg ◽  
Renata Varnaitė ◽  
Wanda Christ ◽  
Puran Chen ◽  
Jagadeeswara R. Muvva ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cellular Immunity ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Humoral And Cellular Immunity ◽  
Cell Responses

AbstractBackgroundInsights into early, specific humoral and cellular responses to infection with SARS-CoV-2, as well as the persistence and magnitude of resulting immune memory is important amidst the ongoing pandemic. The combination of humoral and cellular immunity will most likely contribute to protection from reinfection or severe disease.MethodsHere, we conducted a longitudinal study on hospitalized moderate and severe COVID-19 patients from the acute phase of disease into convalescence at five- and nine-months post symptom onset. Utilizing flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune memory during and after human SARS-CoV-2 infection.FindingsDuring acute COVID-19, we observed an increase in germinal center activity, a substantial expansion of antibodysecreting cells, and the generation of SARS-CoV-2-neutralizing antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralizing antibody titers as well as robust specific memory B cell responses and polyfunctional T cell responses at five- and nine-months after symptom onset in both moderate and severe COVID-19 patients. Long-term SARS-CoV-2 specific responses were marked by preferential targeting of spike over nucleocapsid protein.ConclusionsOur findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2 specific immunological memory in hospitalized COVID-19 patients long after recovery, likely contributing towards protection against reinfection.

scholarly journals Infection and Immune Memory: Variables in Robust Protection by Vaccines Against SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Pankaj Ahluwalia ◽  
Kumar Vaibhav ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Severe Disease ◽  
Immunological Memory ◽  
Immune Memory ◽  
Erythroid Progenitor ◽  
Cd8 Cells ◽  
Future Design ◽  
Precise Knowledge

SARS-CoV-2 is the cause of a recent pandemic that has led to more than 3 million deaths worldwide. Most individuals are asymptomatic or display mild symptoms, which raises an inherent question as to how does the immune response differs from patients manifesting severe disease? During the initial phase of infection, dysregulated effector immune cells such as neutrophils, macrophages, monocytes, megakaryocytes, basophils, eosinophils, erythroid progenitor cells, and Th17 cells can alter the trajectory of an infected patient to severe disease. On the other hand, properly functioning CD4+, CD8+ cells, NK cells, and DCs reduce the disease severity. Detailed understanding of the immune response of convalescent individuals transitioning from the effector phase to the immunogenic memory phase can provide vital clues to understanding essential variables to assess vaccine-induced protection. Although neutralizing antibodies can wane over time, long-lasting B and T memory cells can persist in recovered individuals. The natural immunological memory captures the diverse repertoire of SARS-CoV-2 epitopes after natural infection whereas, currently approved vaccines are based on a single epitope, spike protein. It is essential to understand the nature of the immune response to natural infection to better identify ‘correlates of protection’ against this disease. This article discusses recent findings regarding immune response against natural infection to SARS-CoV-2 and the nature of immunogenic memory. More precise knowledge of the acute phase of immune response and its transition to immunological memory will contribute to the future design of vaccines and the identification of variables essential to maintain immune protection across diverse populations.

scholarly journals Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Khan ◽  
...  
Keyword(s):  
Antibody Response ◽  
Orange County ◽  
Medical Center ◽  
Natural Infection ◽  
Severe Disease ◽  
Vaccination Campaign ◽  
Cross Reactivity ◽  
Before And After ◽  
Finger Stick ◽  
Antibody Levels

AbstractWe analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

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