scholarly journals Humoral and cellular immune response against SARS-CoV-2 variants following heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination.

Author(s):  
Georg Behrens ◽  
Joana Barros-Martins ◽  
Swantje Hammerschmidt ◽  
Anne Cossmann ◽  
Ivan Odak ◽  
...  

Abstract Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the decision to either receive a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact (CoCo) Study cohort of health care professionals (HCP) to monitor ChAd primed immune responses before and three weeks after booster with ChAd or BioNTech/Pfizer’s BNT162b2. Whilst both vaccines boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

2021 ◽  
Author(s):  
Joana Barros-Martins ◽  
Swantje Hammerschmidt ◽  
Anne Cossmann ◽  
Ivan Odak ◽  
Metodi V Stankov ◽  
...  

Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca's ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the decision to either receive a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School's COVID-19 Contact (CoCo) Study cohort of health care professionals (HCP) to monitor ChAd primed immune responses before and three weeks after booster with ChAd or BioNTech/Pfizer's BNT162b2. Whilst both vaccines boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).


2021 ◽  
Author(s):  
Joana Barros-Martins ◽  
Swantje I. Hammerschmidt ◽  
Anne Cossmann ◽  
Ivan Odak ◽  
Metodi V. Stankov ◽  
...  

AbstractCurrently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer’s BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.


Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 807-814 ◽  
Author(s):  
James W. Lillard ◽  
Udai P. Singh ◽  
Prosper N. Boyaka ◽  
Shailesh Singh ◽  
Dennis D. Taub ◽  
...  

AbstractMacrophage inflammatory protein-1α (MIP-1α) and MIP-1β are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized the affects of MIP-1α and MIP-1β on cellular and humoral immune responses. MIP-1α stimulated strong antigen (Ag)–specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1β promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MIP-1α elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1β only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1β produced higher titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1α. Splenic T cells from MIP-1α– or MIP-1β–treated mice displayed higher Ag-specific Th1 (interferon-γ [IFN-γ]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1β–treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1α–treated mice. However, MIP-1α effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4+ versus CD8+ T cells and modulate CD40, CD80, and CD86 expressed by B220+ cells as well as CD28, 4-1BB, and gp39 expression by CD4+ and CD8+ T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses.


2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.


Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 27 ◽  
Author(s):  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Yosuke Yasui ◽  
Takashi Ito ◽  
Tetsuo Nakayama

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.


Author(s):  
Neil Goldstein ◽  
Viki Bockstal ◽  
Stephan Bart ◽  
Kerstin Luhn ◽  
Cynthia Robinson ◽  
...  

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.


PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192541 ◽  
Author(s):  
Limei Shen ◽  
Stefan Tenzer ◽  
Moritz Hess ◽  
Ute Distler ◽  
Ingrid Tubbe ◽  
...  

2015 ◽  
Vol 112 (15) ◽  
pp. 4719-4724 ◽  
Author(s):  
Anita K. McElroy ◽  
Rama S. Akondy ◽  
Carl W. Davis ◽  
Ali H. Ellebedy ◽  
Aneesh K. Mehta ◽  
...  

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.


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