scholarly journals Evolution of immunity to SARS-CoV-2

2020 ◽  
Author(s):  
Adam K Wheatley ◽  
Jennifer A Juno ◽  
Jing J Wang ◽  
Kevin J Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
Animal Studies ◽  
Vaccine Development ◽  
Natural Infection ◽  
Serum Antibody ◽  
Population Level ◽  
Antibody Responses ◽  
Cell Dynamics ◽  
Specific Memory ◽  
Over Time

The durability of infection-induced SARS-CoV-2 immunity has major implications for public health mitigation and vaccine development. Animal studies and the scarcity of confirmed re-infection suggests immune protection is likely, although the durability of this protection is debated. Lasting immunity following acute viral infection requires maintenance of both serum antibody and antigen-specific memory B and T lymphocytes and is notoriously pathogen specific, ranging from life-long for smallpox or measles4, to highly transient for common cold coronaviruses (CCC). Neutralising antibody responses are a likely correlate of protective immunity and exclusively recognise the viral spike (S) protein, predominantly targeting the receptor binding domain (RBD) within the S1 sub-domain. Multiple reports describe waning of S-specific antibodies in the first 2-3 months following infection. However, extrapolation of early linear trends in decay might be overly pessimistic, with several groups reporting that serum neutralisation is stable over time in a proportion of convalescent subjects. While SARS-CoV-2 specific B and T cell responses are readily induced by infection, the longitudinal dynamics of these key memory populations remains poorly resolved. Here we comprehensively profiled antibody, B and T cell dynamics over time in a cohort recovered from mild-moderate COVID-19. We find that binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection, as expected, with a similar decline in S-specific CD4+ and circulating T follicular helper (cTFH) frequencies. In contrast, S-specific IgG+ memory B cells (MBC) consistently accumulate over time, eventually comprising a significant fraction of circulating MBC. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent subjects to 74 days, with probable additive protection from B and T cells. Overall, our study suggests SARS-CoV-2 immunity after infection is likely to be transiently protective at a population level. SARS-CoV-2 vaccines may require greater immunogenicity and durability than natural infection to drive long-term protection.

scholarly journals Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam K. Wheatley ◽  
Jennifer A. Juno ◽  
Jing J. Wang ◽  
Kevin J. Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Natural Infection ◽  
Population Level ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Specific Igg ◽  
Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

scholarly journals Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Min Zhao ◽  
Junbo Chen ◽  
Shuguang Tan ◽  
Tao Dong ◽  
Hui Jiang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Avian Influenza ◽  
Influenza A ◽  
T Cell Immunity ◽  
H7n9 Virus ◽  
Specific Memory ◽  
Cell Immunity ◽  
H7n9 Infection ◽  
Over Time

ABSTRACT Since 2013, influenza A H7N9 virus has emerged as the most common avian influenza virus subtype causing human infection, and it is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of 45 H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5 to 4 months, 6 to 8 months, and 12 to 15 months postinfection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to the intensive care unit (ICU) and patients presenting with acute respiratory distress syndrome (ARDS) than in patients with mild disease. Frequencies of virus-specific gamma interferon (IFN-γ)-secreting T cells were lower in critically ill patients requiring ventilation than in patients without ventilation within 4 months after infection. The percentages of H7N9-specific IFN-γ-secreting T cells tended to increase over time in patients ≥60 years or in critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were observed at 6 to 8 months after H7N9 infection compared to those in samples obtained at 1.5 to 4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients and have implications for T cell-directed immunization strategies. IMPORTANCE Avian influenza A H7N9 virus remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus-specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were detected at 6 to 8 months after infection. Our results indicated a long-term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, which is relevant to the development of T cell-based universal influenza vaccines.

scholarly journals Subdominance in Antibody Responses: Implications for Vaccine Development

2020 ◽  
Vol 85 (1) ◽  
Author(s):  
Gunnar Lindahl
Keyword(s):  
Cellular Immunity ◽  
Vaccine Development ◽  
Natural Infection ◽  
Antibody Responses ◽  
Protective Antibodies

Vaccines work primarily by eliciting antibodies, even when recovery from natural infection depends on cellular immunity. Large efforts have therefore been made to identify microbial antigens that elicit protective antibodies, but these endeavors have encountered major difficulties, as witnessed by the lack of vaccines against many pathogens. This review summarizes accumulating evidence that subdominant protein regions, i.e., surface-exposed regions that elicit relatively weak antibody responses, are of particular interest for vaccine development.

The Influence of Genetic Variation on the Splenic T Cell Cytokine and Specific Serum Antibody Responses toPorphyromonas gingivalisin Mice

2000 ◽  
Vol 71 (7) ◽  
pp. 1130-1138 ◽  
Author(s):  
Erica Gemmell ◽  
Tracey A. Winning ◽  
Dorothy A. Grieco ◽  
Philip S. Bird ◽  
Gregory J. Seymour
Keyword(s):  
Genetic Variation ◽  
T Cell ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Specific Serum

Analysis of Spontaneous Vs. Vaccine-Induced Antibody Responses Against Cancer-Testis Antigen MAGE-A3 in Cancer Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5087-5087
Author(s):  
Yanran Cao ◽  
Sacha Gnjatic ◽  
Vincent G. Brichard ◽  
Tim Luetkens ◽  
Sebastian Kobold ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Fine Specificity ◽  
Specific Memory ◽  
Cancer Testis

Abstract Abstract 5087 Background: Cancer-testis antigens (CTA) are attractive targets for cancer immunotherapy based on their tumor-restricted expression and immunogenicity. A number of CTA, including Melanoma-associated antigen 3 (MAGE-A3), are already under clinical investigation and CTA have been shown to induce strong T cell and humoral immunity in cancer patients receiving active immunotherapy. However, little is known about the fine specificity and the function of vaccine-induced humoral immune responses and it is unclear how they relate to spontaneous CTA-specific immune responses occurring in a minority of patients. Methods: We have performed a longitudinal analysis of spontaneously occurring antibody responses against the CT antigen MAGE-A3 in sera (N=1537), which were collected from patients with multiple myeloma (N=355) over a period of 6 years. Antibody titers were determined by ELISA technique and a B cell ELISPOT assay was applied to estimate the number of MAGEA3-specific memory B cells in peripheral blood of the patients. Fine specificity of the antibody responses was examined using overlapping 20mer peptides spanning the whole sequence of MAGE-A3. The given IgG subtype was determined, and the quality of MAGE-A3-specific antibodies was analyzed using western blot as well as affinity assays. Results were compared to those obtained with MAGE-A3-specific antibody responses induced by vaccination with full-length MAGE-A3 protein and adjuvants AS02B or AS15 in patients with non-small cell lung cancer (NSCLC; N=15). Results: Out of 355 myeloma patients 4 (1.1%) evidenced spontaneous antibody responses against MAGE-A3 at least at one point during the course of their disease. Spontaneously occurring anti-MAGE-A3 humoral responses were usually of low titer. In contrast, all of the vaccinated patients showed high-titered and persisting antibody responses which usually appeared around week 6 after the first application of the vaccine. Accordingly, we found high frequencies of vaccine-induced MAGE-A3-specific memory B cells in the peripheral blood of NSCLC patients while they remained undetectable in most myeloma patients. Vaccine-induced antibody responses underwent affinity maturation reaching affinity levels of spontaneous immune responses after repeated cycles of treatment. MAGE-A3-specific antibodies consisted of IgG1 and IgG3>IgG2>IgG4 subtypes in vaccinated patients whereas spontaneously occurring antibodies were mainly of the IgG2 subtype. Spontaneous as well as vaccine-induced IgG antibodies both recognized the natural full-length protein. Analysis of the fine specificity of the antibody responses revealed that vaccine-induced antibodies recognized a much larger number of MAGE-A3 epitopes than spontaneously occurring antibodies. However, both, spontaneous as well as vaccine-induced responses, most frequently and strongly recognized a specific region within the MAGE-A3 protein corresponding to amino acids 51–70. Conclusions This study demonstrates for the first time important qualitative differences between spontaneously occurring and vaccine-induced antibody responses against the MAGE-A3 antigen in cancer patients. While the potential of both types of antibody responses to promote antigen uptake and induction of T cell responses by antigen-presenting cells might differ, they both recognized the same restricted region within the MAGE-A3 protein. The latter finding might be of importance for the design of future immunotherapies targeting MAGE-A3. Disclosures: No relevant conflicts of interest to declare.

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 Recombinant Vaccinia Virus Coexpressing the F Protein of Respiratory Syncytial Virus (RSV) and Interleukin-4 (IL-4) Does Not Inhibit the Development of RSV-Specific Memory Cytotoxic T Lymphocytes, whereas Priming Is Diminished in the Presence of High Levels of IL-2 or Gamma Interferon

1998 ◽  
Vol 72 (5) ◽  
pp. 4080-4087 ◽  
Author(s):  
Gary P. Bembridge ◽  
Juan A. Lopez ◽  
Roy Cook ◽  
Jose A. Melero ◽  
Geraldine Taylor
Keyword(s):  
Cytotoxic T Lymphocytes ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Recombinant Vaccinia ◽  
F Protein ◽  
Specific Serum ◽  
Specific Memory ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
Memory Cytotoxic T Lymphocytes

ABSTRACT In order to investigate if immune responses to the fusion (F) protein of respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant vaccinia viruses (rVV) carrying both the F gene of RSV and the gene for murine interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-γ) were constructed. In vitro characterization of rVV revealed that insertion of the cytokine gene into the VP37 locus of the vaccinia virus genome resulted in 100- to 1,000-fold higher expression than insertion of the same gene into the thymidine kinase (TK) locus. In comparison, only a two- to fivefold difference in the level of expression of the F protein was observed when the gene was inserted into either of these two loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-γ cleared rVV more rapidly than mice inoculated with a control rVV and developed only low levels of RSV-specific serum antibody. In addition, these recombinants were much less effective at priming RSV-specific memory cytotoxic T lymphocytes (CTL) and IFN-γ production by spleen cells than rVV expressing the F protein alone. In contrast, mice vaccinated with rVV expressing high levels of IL-4 showed signs of delayed rVV clearance. RSV-specific serum antibody responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as there was a significant reduction in IgG2a antibody responses compared with serum antibody responses in mice vaccinated with rVV expressing the F protein alone. However, vaccination with rVV expressing the F protein together with high levels of IL-4 did not alter the development of RSV-specific memory CTL or IFN-γ production by RSV-restimulated splenocytes.

Development of an effective vaccination protocol to produce Salmonella-free layer fock

2021 ◽  
Vol 1 (2) ◽  
pp. 1-6
Author(s):  
Taslima Akter ◽  
Mohammed Nooruzzaman ◽  
Tanjin T. Mumu ◽  
Mustak Ahammed ◽  
ABM Jalal Uddin ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Salmonella Spp ◽  
Salmonella Gallinarum ◽  
Booster Immunization ◽  
Vaccination Protocol ◽  
Salmonella Infections ◽  
Positive Rate ◽  
Over Time

Salmonella infections are of prime importance in the layer chicken industry and pose a significant public health threat. Production of export quality poultry products requires Salmonella-free certification. We developed and applied a vaccination schedule based on a commercial live attenuated Salmonella enterica serovar Gallinarum biovar Gallinarum (S. Gallinarum) vaccine in a layer flock. A flock of 1000 ISA Brown chickens has vaccinated with a lyophilized fowl typhoid live vaccine at definite time intervals. Isolation of Salmonella spp. in cloacal swabs and detection of serum antibody responses were performed using serum plate agglutination (SPA) test and ELISA. At the time of vaccination (16 weeks (w) of age), 50% of the tested birds carried Salmonella spp. in feces. Following booster immunization at 18 w, 21 w, and then every 12 weeks interval, the shedding of Salmonella decreased significantly over time with 40% at 21 w, 10% at 30 w, and 5% each at 42 and 54 w, and no shedding was detected at 66 and 78 w. Biochemical analysis of 32 Salmonella isolates revealed 15.6% (n=5) Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum), 37.5% (n=12) Salmonella Gallinarum, and 46.9% (n=15) paratyphoid causing Salmonella. Of note, the Salmonella spp. detected after 21 w of age belonged to the paratyphoid group. The decreased shedding of bacteria paralleled with increased antibody responses. The antibody level at vaccination (20% positive rate at 16 w) increased over time with a 50% positive rate at 18 w, 80% at 42 w, 90% at 54 w, and 100% at 66 w and 78 w by serum plate agglutination (SPA) test. Similarly, the serum antibody levels of chickens were also measured using ELISA and were similar to the SPA test. In conclusion, the vaccine schedule developed in this study confirmed a high seroconversion and prevented Salmonella shedding in feces. Therefore, a three-month interval vaccination protocol from the pre-laying stage to the last stage of laying is recommended to prevent Salmonella infections in laying flocks.

scholarly journals Antibody and T cell responses to Sinopharm/BBIBP-CorV in naive and previously infected individuals in Sri Lanka

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Inoka Sepali Aberathna ◽  
Pradeep Dharshana Pushpakumara ◽  
Achala Kamaladasa ◽  
Dinuka Guruge ◽  
...  
Keyword(s):  
T Cell ◽  
Sri Lanka ◽  
Ex Vivo ◽  
Natural Infection ◽  
T Cell Responses ◽  
Antibody Responses ◽  
Receptor Blocking ◽  
Cell Responses ◽  
Antibody Titres ◽  
Blocking Antibodies

Background: As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. Methods: SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor binding domain (RBD) of the wild type (WT), B.1.1.7, B.1.351 and B.1.617.2, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 weeks and at 6 weeks (2 weeks after the second dose). Results: 95% of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p<0.001) in individuals >60 years (93.3%) compared to those who were 20 to 39 years (98.9%). 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p=0.44). Vaccinees had significantly less (p<0.0001) antibodies to the RBD of WT and B.1.1.7, although there was no difference in antibodies to the RBD of B.1.351 and B.1.617.2 compared to convalescent sera. 27.7% of 46.4% of vaccinees had ex vivo IFNγ and cultured ELISpot responses respectively, and IFNγ and CD107a responses were detected by flow cytometry. Conclusions: Sinopharm/BBIBP-CorV appeared to induce high seroconversion rates and induce a similar level of antibody responses against ACE2 receptor, B.1.617.2 and B.1.351 as seen following natural infection.

Serum antibody responses in sheep after natural infection with Bacteroides nodosus

2010 ◽  
Vol 67 (3) ◽  
pp. 98-101 ◽  
Author(s):  
RJ Whittington ◽  
DJ Marshall ◽  
RI Walker ◽  
MJ Turner
Keyword(s):  
Natural Infection ◽  
Serum Antibody ◽  
Antibody Responses
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