scholarly journals A measles-vectored COVID-19 vaccine induces long-term immunity and protection from SARS-CoV-2 challenge in mice

2021 ◽  
Author(s):  
Phanramphoei N. Frantz ◽  
Aleksandr Barinov ◽  
Claude Ruffié ◽  
Chantal Combredet ◽  
Valérie Najburg ◽  
...  

AbstractIn light of the expanding SARS-CoV-2 pandemic, developing efficient vaccines that can provide sufficient coverage for the world population is a global health priority. The measles virus (MV)-vectored vaccine is an attractive candidate given the measles vaccine’s extensive safety history, well-established manufacturing process, and induction of strong, long-lasting immunity. We developed an MV-based SARS-CoV-2 vaccine using either the full-length spike (S) or S2 subunit as the antigen. While the S2 antigen failed to induce neutralizing antibodies, the prefusion-stabilized, full-length S (MV-ATU2-SF-2P-dER) construct proved to be an attractive vaccine candidate, eliciting strong Th1-dominant T-cell and neutralizing antibody responses against the S antigen while minimizing reactivity to the vector itself. Neutralizing antibody titers remained high three months after homologous prime-boost immunization, and infectious virus was undetectable in all animals after challenge with a mouse-adapted SARS-CoV-2 virus.

2021 ◽  
Author(s):  
Chanukya GV ◽  
Aparna Srikantam

In COVID 19 pandemic, first line of defense is effective vaccination program. Because of multiple platforms available for vaccine production we tested relative immunogenicity of two vaccines available in India, Covaxin and Covishield We performed quantitative analysis of neutralizing antibodies to SARS Cov2 spike (receptor binding domain ) protein, from sera of 53 subjects who completed vaccines schedules. There was significantly higher immunogenic response with Covishield as compared to Covaxin and are independent of age. Studies on a large scale with long term follow up are needed to further advance the knowledge in this domain.


2019 ◽  
Vol 220 (4) ◽  
pp. 594-602 ◽  
Author(s):  
Iris D Brinkman ◽  
Jelle de Wit ◽  
Gaby P Smits ◽  
Hinke I ten Hulscher ◽  
Maria C Jongerius ◽  
...  

AbstractBackgroundThe majority of infants will not be protected by maternal antibodies until their first measles vaccination, between 12 and 15 months of age. This provides incentive to reduce the age at measles vaccination, but immunological consequences are insufficiently understood, and long-term effects are largely unknown.MethodsA total of 79 infants who received early measles vaccination between 6 and 12 months age and a second dose at 14 months of age were compared to 44 children in a control group who received 1 dose at 14 months of age. Measles virus–specific neutralizing antibody concentrations and avidity were determined up to 4 years of age.ResultsInfants who first received measles vaccination before 12 months of age had a long-term decrease in the concentration and avidity of measles virus–specific neutralizing antibodies, compared with infants in the control group. For 11.1% of children with a first dose before 9 months of age, antibody levels at 4 years of age had dropped below the cutoff for clinical protection.ConclusionsEarly measles vaccination provides immediate protection in the majority of infants but yields a long-term decrease in neutralizing antibody responses, compared to vaccination at a later age. Additional vaccination at 14 months of age does not improve this. Over the long term, this may result in an increasing number of children susceptible to measles.


2021 ◽  
Author(s):  
Julie Demaret ◽  
Benedicte Corroyer-Simovic ◽  
Enagnon Kazali Alidjinou ◽  
Anne Goffard ◽  
Jacques Trauet ◽  
...  

We quantified S1-specific IgG, neutralizing antibody titers, specific IFNγ secreting T cells and functionality of specific CD4+ and CD8+ T cells in 130 young adults (median age 44.0 years) and 106 older residents living in a long-term care facility (86.5 years) after 2 doses of BNT162b2. Three months after the first injection, humoral and cellular memory responses were dramatically impaired in the 54 COVID-19-naive older compared to the 121 COVID 19 naive younger adults. Notably, older participants' neutralizing antibodies, detected in 76.5% (versus 100% in young adults, P < 0.0001), were ten times lower than the younger's antibody titers (P < 0.0001). Antibody and T cell responses were greater among the 52 COVID 19-recovered than among the 54 COVID-19-naive older adults (P < 0.0001). Our study shows that 2 doses of BNT162b2 does not guarantee long-term protection against SARS-CoV-2 in the older. An additional dose should be considered to boost their specific memory response.


2021 ◽  
Vol 12 ◽  
Author(s):  
Atsushi Goto ◽  
Hirofumi Go ◽  
Kei Miyakawa ◽  
Yutaro Yamaoka ◽  
Norihisa Ohtake ◽  
...  

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19.Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients’ characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20–32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman’s correlation.Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147–224); median [range] years of age, 50 (20–78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman’s correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig).Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.


Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shiho Chiba ◽  
Steven J. Frey ◽  
Peter J. Halfmann ◽  
Makoto Kuroda ◽  
Tadashi Maemura ◽  
...  

AbstractThe COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.


2007 ◽  
Vol 88 (2) ◽  
pp. 621-630 ◽  
Author(s):  
S. Maan ◽  
N. S. Maan ◽  
A. R. Samuel ◽  
S. Rao ◽  
H. Attoui ◽  
...  

The outer capsid protein VP2 of Bluetongue virus (BTV) is a target for the protective immune response generated by the mammalian host. VP2 contains the majority of epitopes that are recognized by neutralizing antibodies and is therefore also the primary determinant of BTV serotype. Full-length cDNA copies of genome segment 2 (Seg-2, which encodes VP2) from the reference strains of each of the 24 BTV serotypes were synthesized, cloned and sequenced. This represents the first complete set of full-length BTV VP2 genes (from the 24 serotypes) that has been analysed. Each Seg-2 has a single open reading frame, with short inverted repeats adjacent to conserved terminal hexanucleotide sequences. These data demonstrated overall inter-serotype variations in Seg-2 of 29 % (BTV-8 and BTV-18) to 59 % (BTV-16 and BTV-22), while the deduced amino acid sequence of VP2 varied from 22.4 % (BTV-4 and BTV-20) to 73 % (BTV-6 and BTV-22). Ten distinct Seg-2 lineages (nucleotypes) were detected, with greatest sequence similarities between those serotypes that had previously been reported as serologically ‘related’. Fewer similarities were observed between different serotypes in regions of VP2 that have been reported as antigenically important, suggesting that they may play a role in the neutralizing antibody response. The data presented form an initial basis for BTV serotype identification by sequence analyses and comparison of Seg-2, and for development of molecular diagnostic assays for individual BTV serotypes (by RT-PCR).


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.


2021 ◽  
Author(s):  
Noa Eliakim Raz ◽  
Amos Stemmer ◽  
Yaara Leibovici-Weissman ◽  
Asaf Ness ◽  
Muhammad Awwad ◽  
...  

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.


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