scholarly journals Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao-Lin Jiang ◽  
Guo-Lin Wang ◽  
Xiang-Na Zhao ◽  
Fei-Hu Yan ◽  
Lin Yao ◽  
...  
Keyword(s):  
T Cell ◽  
Receptor Binding ◽  
Symptom Onset ◽  
T Cell Responses ◽  
Receptor Binding Domain ◽  
Neutralising Antibodies ◽  
Specific Antibodies ◽  
Cell Responses ◽  
Protein Receptor ◽  
Nucleoprotein N

AbstractThe dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15–30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3–4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3–4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3–4 months after infection.

scholarly journals Single dose immunization with a COVID-19 DNA vaccine encoding a chimeric homodimeric protein targeting receptor binding domain (RBD) to antigen-presenting cells induces rapid, strong and long-lasting neutralizing IgG, Th1 dominated CD4+ T cells and strong CD8+ T cell responses in mice

2020 ◽  
Author(s):  
Gunnstein Norheim ◽  
Elisabeth Stubsrud ◽  
Lise Madelene Skullerud ◽  
Branislava Stankovic ◽  
Stalin Chellappa ◽  
...  
Keyword(s):  
T Cells ◽  
Single Dose ◽  
T Cell ◽  
Receptor Binding ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Cell Responses ◽  
Antigen Presenting

AbstractThe pandemic caused by the SARS-CoV-2 virus in 2020 has led to a global public health emergency, and non-pharmaceutical interventions required to limit the viral spread are severely affecting health and economies across the world. A vaccine providing rapid and persistent protection across populations is urgently needed to prevent disease and transmission. We here describe the development of novel COVID-19 DNA plasmid vaccines encoding homodimers consisting of a targeting unit that binds chemokine receptors on antigen-presenting cells (human MIP-1α /LD78β), a dimerization unit (derived from the hinge and CH3 exons of human IgG3), and an antigenic unit (Spike or the receptor-binding domain (RBD) from SARS-CoV-2). The candidate encoding the longest RBD variant (VB2060) demonstrated high secretion of a functional protein and induced rapid and dose-dependent RBD IgG antibody responses that persisted up to at least 3 months after a single dose of the vaccine in mice. Neutralizing antibody (nAb) titers against the live virus were detected from day 7 after one dose. All tested dose regimens reached titers that were higher or comparable to those seen in sera from human convalescent COVID-19 patients from day 28. T cell responses were detected already at day 7, and were subsequently characterized to be multifunctional CD8+ and Th1 dominated CD4+ T cells. Responses remained at sustained high levels until at least 3 months after a single vaccination, being further strongly boosted by a second vaccination at day 89. These findings, together with the simplicity and scalability of plasmid DNA manufacturing, safety data on the vaccine platform in clinical trials, low cost of goods, data indicating potential long term storage at +2° to 8°C and simple administration, suggests the VB2060 candidate is a promising second generation candidate to prevent COVID-19.

scholarly journals SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence

2021 ◽  
Vol 17 (7) ◽  
pp. e1009761
Author(s):  
Sushma Boppana ◽  
Kai Qin ◽  
Jacob K. Files ◽  
Ronnie M. Russell ◽  
Regina Stoltz ◽  
...  
Keyword(s):  
T Cell ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
S Protein ◽  
Cell Responses ◽  
Helper Cells ◽  
Follicular Helper

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.

scholarly journals Heterologous vaccination with inactivated and mRNA vaccines increases B and T cell responses to SARS-CoV-2

2022 ◽  
Author(s):  
Fanglei Zuo ◽  
Hassan Abolhassani ◽  
Likun Du ◽  
Antonio Piralla ◽  
Federico Bertoglio ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Infection ◽  
T Cell Responses ◽  
Wild Type Virus ◽  
Wild Type ◽  
Specific Antibodies ◽  
Cell Responses ◽  
Specific Memory ◽  
Boost Immunization ◽  
Inactivated Vaccines

Abstract Background There has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. Methods The levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples. Results A booster dose of an mRNA vaccine significantly increased the specific antibody response to the wild-type and VOCs including Omicron (by 14-fold), in individuals who had previously received two doses of inactivated vaccines. The levels of specific antibodies in the heterologous vaccination group were similar to those in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Furthermore, this heterologous vaccination regime significantly improved the specific memory B and T cell responses. Conclusions Heterologous prime-boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.

scholarly journals Polymersomes decorated with SARS-CoV-2 spike protein receptor binding domain elicit robust humoral and cellular immunity

2021 ◽  
Author(s):  
Lisa R Volpatti ◽  
Rachel P Wallace ◽  
Shijie Cao ◽  
Michal Raczy ◽  
Ruyi Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Response ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Vaccination Site ◽  
Monophosphoryl Lipid A ◽  
Protein Receptor

A diverse portfolio of SARS-CoV-2 vaccine candidates is needed to combat the evolving COVID-19 pandemic. Here, we developed a subunit nanovaccine by conjugating SARS-CoV-2 Spike protein receptor binding domain (RBD) to the surface of oxidation-sensitive polymersomes. We evaluated the humoral and cellular responses of mice immunized with these surface-decorated polymersomes (RBDsurf) compared to RBD-encapsulated polymersomes (RBDencap) and unformulated RBD (RBDfree), using monophosphoryl lipid A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBDsurf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBDsurf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBDsurf and RBDencap drove similarly robust CD4+ and CD8+ T cell responses that produced multiple Th1-type cytokines. We conclude that multivalent surface display of Spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses

2021 ◽  
Author(s):  
Harikrishnan Balachandran ◽  
Chansavath Phetsouphanh ◽  
David Agapiou ◽  
Anurag Adhikari ◽  
Chaturaka Rodrigo ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Post Infection ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Cd4 T Cell ◽  
Neutralising Antibodies ◽  
Cell Responses

scholarly journals Cellular and Humoral Immunity to Ebola Zaire Glycoprotein and Viral Vector Proteins Following Immunization with Recombinant Vesicular Stomatitis Virus-Based Ebola Vaccine (rVSV∆G-EBOV-GP)

2021 ◽  
Author(s):  
Vanessa N Raabe ◽  
Lilin Lai ◽  
Juliet Morales ◽  
Yongxian Xu ◽  
Nadine Rouphael ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Vesicular Stomatitis Virus ◽  
Matrix Protein ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Post Vaccination ◽  
Cell Responses ◽  
Vesicular Stomatitis ◽  
Nucleoprotein N

While effective at preventing Zaire ebolavirus (EBOV) disease, cellular immunity to EBOV and vector-directed immunity elicited by the recombinant vesicular stomatitis virus expressing Ebola glycoprotein (rVSVΔG-EBOV-GP) vaccine remains poorly understood. Sera and peripheral blood mononuclear cells were collected from 32 participants enrolled in a prospective multicenter study [ClinicalTrials.gov NCT02788227] before vaccination and up to six months post-vaccination. IgM and IgG antibodies, IgG-producing memory B cells, and T cell reactivity to EBOV glycoprotein, vesicular stomatitis virus-Indiana strain (VSV-I) matrix protein, and VSV-I nucleoprotein were measured using ELISA, ELISpot, and intracellular cytokine staining, respectively. Eleven participants previously received a different investigational Ebola vaccine. All participants met positivity criteria for IgG antibodies to, and circulating IgG-producing memory B cells to, EBOV glycoprotein following rVSVΔG-EBOV-GP vaccination. Transient IgM and IgG antibody responses to VSV-I matrix protein (n=1/32 and n=0/32, respectively) and nucleoprotein (n=2/32 and n=1/32, respectively) were infrequently detected, as were IgG-producing memory B cells recognizing VSV-I matrix protein (n=3/31) and nucleoprotein (n=2/31). CD4+ and CD8+ T cell responses to EBOV glycoprotein were present in 15/32 and 19/32 participants at baseline and in 32/32 and 23/32 participants one month post-vaccination, respectively. CD4+ and CD8+ T cell responses to VSV-I matrix protein (n=17/32 and n=16/32, respectively) and VSV-I nucleoprotein (n=23/32 for both CD4+ and CD8+ responses) were common post-vaccination. T cell responses were predominantly mono-cytokine, except CD8+ responses to EBOV glycoprotein among heterologous Ebola vaccine-experienced participants and CD8+ responses to VSV-I nucleoprotein. Overall, rVSVΔG-EBOV-GP elicits robust humoral and memory B cell responses to EBOV glycoprotein in both Ebola vaccine-naïve and heterologous Ebola vaccine-experienced individuals and can generate vector-directed T cell immunity. Further research is needed to understand the significance of pre-existing vector-directed immunity on responses to booster doses of rVSVΔG-EBOV-GP and other rVSV-vectored vaccines.

scholarly journals Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion

2020 ◽  
Author(s):  
Floriane Gallais ◽  
Aurélie Velay ◽  
Marie-Josée Wendling ◽  
Charlotte Nazon ◽  
Marialuisa Partisani ◽  
...  
Keyword(s):  
T Cell ◽  
Symptom Onset ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Serological Tests ◽  
Past Infection ◽  
Cell Responses ◽  
Patient Reported ◽  
Cellular Immune

AbstractBackgroundIn the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results.MethodsHere we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls.ResultsAll index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection.ConclusionExposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus.

scholarly journals CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses

2012 ◽  
Vol 25 (3) ◽  
pp. 89-96 ◽  
Author(s):  
I. B. Rasmussen ◽  
I. Oynebraten ◽  
L. S. Hoydahl ◽  
M. Flobakk ◽  
E. Lunde ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Specific Antibodies ◽  
Cell Responses ◽  
Constant Domains
Sign in / Sign up

Export Citation Format

Share Document