scholarly journals Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

2021 ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract Background Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’. Objectives We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot. Results Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022). Conclusion Dual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals Durable Humoral and Cellular Immune Responses Following Ad26.COV2.S Vaccination for COVID-19

2021 ◽  
Author(s):  
Dan H. Barouch ◽  
Kathryn Stephenson ◽  
Jerald Sadoff ◽  
Jingyou Yu ◽  
Aiquan Chang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Single Shot ◽  
Efficacy Data ◽  
Vaccine Regimen ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported. We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5x10^10 vp or 10^11 vp Ad26.COV2.S and in 5 participants who received placebo. We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens. We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).

scholarly journals Natural and vaccine-induced antibody and cellular responses against emerging SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antibody Neutralization ◽  
Potential Threat ◽  
Cell Responses ◽  
The Uk ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.

scholarly journals DNA Vaccines for Influenza Virus: Differential Effects of Maternal Antibody on Immune Responses to Hemagglutinin and Nucleoprotein

2000 ◽  
Vol 74 (17) ◽  
pp. 7787-7793 ◽  
Author(s):  
Tamera M. Pertmer ◽  
Alp E. Oran ◽  
Janice M. Moser ◽  
Catherine A. Madorin ◽  
Harriet L. Robinson
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Cellular Responses ◽  
Active Immunization ◽  
Antibody Responses ◽  
Maternal Antibody ◽  
Cell Responses ◽  
Influenza Virus Hemagglutinin ◽  
Neonatal Immune System ◽  
Humoral Responses

ABSTRACT Maternal antibody is the major form of protection from disease in early life when the neonatal immune system is still immature; however, the presence of maternal antibody also interferes with active immunization, placing infants at risk for severe bacterial and viral infection. We tested the ability of intramuscular and gene gun immunization with DNA expressing influenza virus hemagglutinin (HA) and nucleoprotein (NP) to raise protective humoral and cellular responses in the presence or absence of maternal antibody. Neonatal mice born to influenza virus-immune mothers raised full antibody responses to NP but failed to generate antibody responses to HA. In contrast, the presence of maternal antibody did not affect the generation of long-lived CD8+ T-cell responses to both HA and NP. Thus, maternal antibody did not affect cell-mediated responses but did affect humoral responses, with the ability to limit the antibody response correlating with whether the DNA-expressed immunogen was localized in the plasma membrane or within the cell.

scholarly journals Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2

2021 ◽  
Vol 14 (1) ◽  
pp. 39
Author(s):  
Iman Almansour ◽  
Nabela Calamata Macadato ◽  
Thamer Alshammari
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Serum Levels ◽  
Antibody Responses ◽  
Limited Data ◽  
Effective Measure ◽  
Vaccine Candidates ◽  
Cellular Immune

Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies.

scholarly journals Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern.

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antibody Neutralization ◽  
Potential Threat ◽  
Cell Responses ◽  
The Uk ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.Authorship note: Donal T. Skelly and Adam C. Harding contributed equally; Miles W. Carroll and William S. James contributed equally

scholarly journals Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Alexander C. Dowell ◽  
Megan S. Butler ◽  
Elizabeth Jinks ◽  
Gokhan Tut ◽  
Tara Lancaster ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Spike Protein ◽  
Cell Responses ◽  
Clinical Protection ◽  
Pediatric Vaccination ◽  
Insight Into

AbstractSARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

scholarly journals Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra J. Spencer ◽  
Paul F. McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D. Bissett ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cytotoxic T Cells ◽  
Antibody Responses ◽  
Limited Data ◽  
Vectored Vaccine ◽  
Cellular Immune

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

scholarly journals Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
Author(s):  
Spencer W. Stonier ◽  
Andrew S. Herbert ◽  
Ana I. Kuehne ◽  
Ariel Sobarzo ◽  
Polina Habibulin ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Ebola Virus ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

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