scholarly journals Can individuals with low antibody responses to vaccines against other viruses acquire adequate SARS-CoV-2 antibody after vaccination with the BNT162b2 mRNA vaccine?

2021 ◽  
Author(s):  
Wataru Ogura ◽  
Kouki Ohtsuka ◽  
Sachiko Matsuura ◽  
Takahiro Okuyama ◽  
Satsuki Matsushima ◽  
...  
Keyword(s):  
Cohort Study ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Antibody Activity ◽  
Low Responders ◽  
Before And After ◽  
Positive Threshold ◽  
Antibody Levels

Objective In Japan, healthcare workers (HCWs) are vaccinated against coronavirus disease (COVID-19) and other contagious viruses (measles, rubella, chickenpox, mumps, and hepatitis B) to prevent nosocomial infection. However, some do not produce sufficient antibodies after vaccination (low responders). This study investigated changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels among HCWs after SARS-CoV-2 vaccination and assessed whether low responders produced adequate SARS-CoV-2 anti-spike and neutralizing antibodies. Methods We conducted a prospective cohort study of HCWs before and after vaccination with the BNT162b2 mRNA vaccine in a hospital in Tokyo, Japan. The HCWs received two doses of BNT162b2 vaccine, 3 weeks apart. Those whose antibody levels against previous antiviral vaccines did not reach protective antibody levels after receiving two doses were defined as low responders, whereas those who produced adequate antibodies were defined as normal responders. SARS-CoV-2 anti-spike antibodies were measured 11 times from before the first BNT162b2 vaccination to 5 months after the second vaccination. SARS-CoV-2 neutralizing antibody activity was measured twice in low responders, 1 week to 1 month and 5 months after the second vaccination. Results Fifty HCWs were included in the analytic cohort. After vaccination, SARS-CoV-2 anti-spike antibody was detectable in the samples from both responders at each timepoint, but the level was lower at 5 months than at 1 week after the second vaccination. Low responders had SARS-CoV-2 neutralizing antibody activity 1 week to 1 month after the second vaccination, which exceeded the positive threshold after 5 months. Conclusion After BNT162b2 vaccination, low responders acquired adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies to prevent SARS-CoV-2. However, SARS-CoV-2 anti-spike antibody levels were lower at 5 months than at 1 week after the second dose of BNT162b2 vaccine in low and normal responders. Therefore, low responders should also receive a third dose of BNT162b2 vaccine.

scholarly journals Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

2020 ◽  
Author(s):  
Renata Varnaitė ◽  
Marina García ◽  
Hedvig Glans ◽  
Kimia T. Maleki ◽  
John Tyler Sandberg ◽  
...  
Keyword(s):  
B Cell ◽  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
B Cell Activation ◽  
Immunological Parameters ◽  
Antibody Secreting Cell ◽  
Antibody Levels

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.

scholarly journals Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

2021 ◽  
Author(s):  
Alena J. Markmann ◽  
Natasa Giallourou ◽  
D. Ryan Bhowmik ◽  
Yixuan J. Hou ◽  
Aaron Lerner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Human Antibody ◽  
Antibody Titers ◽  
Sex Disparities ◽  
Binding Antibody ◽  
Male Sex ◽  
Antibody Levels ◽  
First Time

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

scholarly journals Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID-19 Patients

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
Larry L. Luchsinger ◽  
Brett P. Ransegnola ◽  
Daniel K. Jin ◽  
Frauke Muecksch ◽  
Yiska Weisblum ◽  
...  
Keyword(s):  
New York ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Pseudotyped Virus ◽  
Antibody Activity ◽  
Plasma Samples ◽  
Serological Tests ◽  
Population Immunity ◽  
Therapeutic Trials ◽  
Antibody Levels

ABSTRACT The development of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following infection or vaccination is likely to be critical for the development of sufficient population immunity to drive cessation of the coronavirus disease of 2019 (COVID-19) pandemic. A large number of serologic tests, platforms, and methodologies are being employed to determine seroprevalence in populations to select convalescent plasma samples for therapeutic trials and to guide policies about reopening. However, the tests have substantial variations in sensitivity and specificity, and their ability to quantitatively predict levels of NAbs is unknown. We collected 370 unique donors enrolled in the New York Blood Center Convalescent Plasma Program between April and May of 2020. We measured levels of antibodies in convalescent plasma samples using commercially available SARS-CoV-2 detection tests and in-house enzyme-linked immunosorbent assays (ELISAs) and correlated serological measurements with NAb activity measured using pseudotyped virus particles, which offer the most informative assessment of antiviral activity of patient sera against viral infection. Our data show that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have various degrees of accuracy in predicting NAb activity. We found that the Ortho anti-SARS-CoV-2 total Ig and IgG high-throughput serological assays (HTSAs) and the Abbott SARS-CoV-2 IgG assay quantify levels of antibodies that strongly correlate with the results of NAb assays and are consistent with gold standard ELISA results. These findings provide immediate clinical relevance to serology results that can be equated to NAb activity and could serve as a valuable roadmap to guide the choice and interpretation of serological tests for SARS-CoV-2.

scholarly journals A Simple and High-Throughput ELISA-Based Neutralization Assay for the Determination of Anti-Flavivirus Neutralizing Antibodies

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 297
Author(s):  
Jean Claude Balingit ◽  
Minh Huong Phu Ly ◽  
Mami Matsuda ◽  
Ryosuke Suzuki ◽  
Futoshi Hasebe ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Clinical Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Activity ◽  
Vaccine Trials ◽  
Antibody Levels ◽  
Flavivirus Infection

Mosquito-borne flavivirus infections, including dengue virus and Zika virus, are major public health threats globally. While the plaque reduction neutralization test (PRNT) is considered the gold standard for determining neutralizing antibody levels to flaviviruses, the assay is time-consuming and laborious. This study, therefore, aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based microneutralization test (EMNT) for the detection of neutralizing antibodies to mosquito-borne flaviviruses. The inhibition of viral growth due to neutralizing antibodies was determined colorimetrically by using EMNT. Given the significance of Fcγ-receptors (FcγR) in antibody-mediated neutralization and antibody-dependent enhancement (ADE) of flavivirus infection, non-FcγR and FcγR-expressing cell lines were used in the EMNT to allow the detection of the sum of neutralizing and immune-enhancing antibody activity as the neutralizing titer. Using anti-flavivirus monoclonal antibodies and clinical samples, the utility of EMNT was evaluated by comparing the end-point titers of the EMNT and the PRNT. The correlation between EMNT and PRNT titers was strong, indicating that EMNT was robust and reproducible. The new EMNT assay combines the biological functional assessment of virus neutralization activity and the technical advantages of ELISA and, is simple, reliable, practical, and could be automated for high-throughput implementation in flavivirus surveillance studies and vaccine trials.

scholarly journals 453. Neutralizing Antibody Responses to SARS-CoV-2 in Professional Soccer Players

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S327-S328
Author(s):  
Jorge Pagura ◽  
Clovis Arns de Cunha ◽  
Roberto Nishimura ◽  
Sergio Wey ◽  
André Pedrinelli ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Test ◽  
Antibody Responses ◽  
Soccer Players ◽  
P Value ◽  
Rt Pcr ◽  
Professional Soccer ◽  
Antibody Levels ◽  
Pcr Test

Abstract Background The Brazilian Football Confederation (CBF) protocol to control the spread of COVID-19 among professional soccer players is based on four cornerstone measures: (1) Tracing all symptomatic and asymptomatic COVID-19 cases by clinical monitoring and nasal swab SARS-CoV-2 RT-PCR testing up to 3 days before the soccer games; (2) Respiratory isolation of all SARS-CoV-2 positive players for at least 10 days, regardless symptoms; (3) All player with clinical suspicion of COVID-19 were immediately quarantined; (4) If a player became SARS-CoV-2 positive after the game, the other players were allowed to play the next game, if they remained asymptomatic and SARS-CoV-2 RT-PCR negative. Understanding how antibody responses to SARS-CoV-2 evolve can provide insights into therapeutic and testing approaches for COVID-19. In the present study we profile the antibody responses of players up to nine months from a SARS-CoV-2 positive RT-PCR test. Methods Serum samples were obtained from 955 soccer players, and analyzed at the same laboratory in São Paulo city, in the Hospital Israelita Albert Einstein. It was used the cPas Technology, the sVNT kit for detecting and measuring circulating neutralizing antibodies against the SARS-CoV-2 virus. Results Neutralizing antibody was positive for 416 samples (416/955=44%; C.I. 95%= [40%; 47%]). From the 955 soccer players, 454 had RT-PCR+ previously, up to nine months until the neutralizing antibody tests. From this 454 players, 172 (38%) had neutralizing antibody below 20% (C.I. 95% = [34%; 42%]), 30 (7%) between 20% and 30% (C.I. 95% = [5%; 9%]), and e 252 (56%) above 30% (C.I. 95% =[51%; 60%]). Antibody responses to SARS-CoV-2 were significantly higher in individuals RT-PCR+ (Table 1). There was no difference between the neutralizing antibody responses status to SARS-CoV-2 and the time between the RT-PCR+ and the neutralizing antibody test (p-value = 0.423; Figures 1 and 2, Table 2). Table 1. Neutralizing antibody responses to SARS-CoV-2. Figure 1. Scatter plot with Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Table 2. Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Conclusion This study found neutralizing activity of infection against SARS-CoV-2 in 63% RT-PCR+ individuals, but only in 26% in RT-PCR(-) players. Level of neutralizing antibody responses maintained stable until up to nine months after a RT-PCR+. Figure 2. Percentage of soccer players at each antibody level (below 20%, between 20% and 30%, and above 30%) versus time between the positive RT-PCR test and neutralizing antibody test (days). Disclosures All Authors: No reported disclosures

scholarly journals Heterologous prime-boost vaccination with ChAdOx1 nCoV-19 and BNT162b2 mRNA

2021 ◽  
Author(s):  
Matthias Tenbusch ◽  
Sofie Schumacher ◽  
Emanuel Vogel ◽  
Alina Priller ◽  
Juergen Held ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Immune Protection ◽  
Precautionary Measure ◽  
Antibody Testing ◽  
Boost Vaccination ◽  
Vaccination Scheme ◽  
Antibody Titers ◽  
Antibody Levels

Administration of a first dose of the COVID-19 vaccine ChAdOx1 nCoV-19 (Vaxzevria®, AstraZeneca) is associated with a certain risk for vaccine-induced immune thrombotic thrombocytopenia. Therefore, several countries have recommended replacing the second dose of ChAdOx1 nCoV-19 with an mRNA-based vaccine as a precautionary measure, although data on safety and efficacy of such heterologous prime-boost regimen are sparse. Therefore, vaccinees, who had received a heterologous vaccination using ChAdOx1 nCoV-19 as prime and BNT162b2 (Comirnaty®, BioNTech-Pfizer) mRNA as boost vaccination were offered SARS-CoV-2 antibody testing to quantify their vaccine-induced neutralizing antibody response. The results were compared to cohorts of healthcare workers or volunteers, who received homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination regimens, respectively. A striking increase of vaccine-induced SARS-CoV-2 neutralizing antibody activity was observed in 229 vaccinees that received a BNT162b2 boost 9 to 12 weeks after ChAdOx1 nCoV-19 prime. In our cohort comprising over 480 individuals, the heterologous vaccination scheme induced significantly higher neutralizing antibody titers than homologous ChAdOx1 nCoV-19 and even than homologous BNT162b2 vaccination. This proves that a single dose of a COVID-19 mRNA vaccine after ChAdOx1 nCoV-19 prime vaccination is sufficient to achieve high neutralizing antibody levels predicting immune protection from SARS-CoV-2 infection, and may even increase vaccine efficacy offering an alternative in a setting of vaccine shortage.

scholarly journals Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stéphane Marot ◽  
◽  
Isabelle Malet ◽  
Valentin Leducq ◽  
Karen Zafilaza ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Disease Onset ◽  
Control Measures ◽  
Infection Prevention And Control ◽  
Rapid Decline ◽  
Prevention And Control Measures ◽  
Few Data ◽  
Antibody Levels ◽  
And Control

AbstractThere are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.

scholarly journals Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses

2008 ◽  
Vol 82 (12) ◽  
pp. 5912-5921 ◽  
Author(s):  
Zane Kraft ◽  
Katharine Strouss ◽  
William F. Sutton ◽  
Brad Cleveland ◽  
For Yue Tso ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Neutralizing Antibodies ◽  
Acute Infection ◽  
Variable Region ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Virus Envelope ◽  
Variable Regions ◽  
Clade B ◽  
Region Length

ABSTRACT The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against “easy-to-neutralize” clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs.

scholarly journals Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope

2015 ◽  
Vol 89 (16) ◽  
pp. 8130-8151 ◽  
Author(s):  
Katie M. Kilgore ◽  
Megan K. Murphy ◽  
Samantha L. Burton ◽  
Katherine S. Wetzel ◽  
S. Abigail Smith ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Nonhuman Primate ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Cd40 Ligand ◽  
Antibody Activity ◽  
Immunodeficiency Virus ◽  
Antibody Profile ◽  
Hiv 1

ABSTRACTAntibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (HIV-1) vaccine. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. However, these trials often rely on a limited selection of SIV strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. To mirror the viral panels used to assess HIV-1 antibody breadth, we created and characterized a novel panel of 14 genetically and phenotypically diverse SIVsm envelope (Env) glycoproteins. To assess the utility of this panel, we characterized the neutralizing activity elicited by four SIVmac239 envelope-expressing DNA/modified vaccinia virus Ankara vector- and protein-based vaccination regimens that included the immunomodulatory adjuvants granulocyte-macrophage colony-stimulating factor, Toll-like receptor (TLR) ligands, and CD40 ligand. The SIVsm Env panel exhibited a spectrum of neutralization sensitivity to SIV-infected plasma pools and monoclonal antibodies, allowing categorization into three tiers. Pooled sera from 91 rhesus macaques immunized in the four trials consistently neutralized only the highly sensitive tier 1a SIVsm Envs, regardless of the immunization regimen. The inability of vaccine-mediated antibodies to neutralize the moderately resistant tier 1b and tier 2 SIVsm Envs defined here suggests that those antibodies were directed toward epitopes that are not accessible on most SIVsm Envs. To achieve a broader and more effective neutralization profile in preclinical vaccine studies that is relevant to known features of HIV-1 neutralization, more emphasis should be placed on optimizing the Env immunogen, as the neutralization profile achieved by the addition of adjuvants does not appear to supersede the neutralizing antibody profile determined by the immunogen.IMPORTANCEMany in the HIV/AIDS vaccine field believe that the ability to elicit broadly neutralizing antibodies capable of blocking genetically diverse HIV-1 variants is a critical component of a protective vaccine. Various SIV-based nonhuman primate vaccine studies have investigated ways to improve antibody-mediated protection against a heterologous SIV challenge, including administering adjuvants that might stimulate a greater neutralization breadth. Using a novel SIV neutralization panel and samples from four rhesus macaque vaccine trials designed for cross comparison, we show that different regimens expressing the same SIV envelope immunogen consistently elicit antibodies that neutralize only the very sensitive tier 1a SIV variants. The results argue that the neutralizing antibody profile elicited by a vaccine is primarily determined by the envelope immunogen and is not substantially broadened by including adjuvants, resulting in the conclusion that the envelope immunogen itself should be the primary consideration in efforts to elicit antibodies with greater neutralization breadth.

scholarly journals The vaccinia-based Sementis Copenhagen Vector COVID-19 vaccine induces broad and durable cellular and humoral immune responses

2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
First Generation ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Antibody Activity ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Heterologous Boost

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.

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