scholarly journals Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

2021 ◽  
Author(s):  
Tsun-Yung Kuo ◽  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Meei-Yun Lin ◽  
Chung-Chin Wu ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Virus Titer ◽  
Neutralizing Antibody ◽  
Protein S ◽  
Protein Subunit ◽  
Live Virus ◽  
The Third ◽  
Severity Of Disease ◽  
Potent Immune Response ◽  
Ancestral Strain

AbstractThe current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines, increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) adjuvanted with CpG 1018 and aluminum hydroxide. Here we used the Delta variant to challenge hamsters innoculated with S-2P based on the ancestral strain or the Beta variant in two-dose or three-dose regimens. Two doses of ancestral S-2P followed by the third dose of Beta variant S-2P was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the ancestral strain as well as all VoCs. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and reduce lung live virus titer. Three doses of vaccination significantly reduced lung viral RNA titer, regardless of using the ancestral or Beta variant S-2P as the third dose. Based on the immunogenicity and viral challenge data, two doses of ancestral S-2P followed by the third dose of Beta variant S-2P could induce broad and potent immune response against the variants.

scholarly journals Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

2021 ◽  
Author(s):  
Xun Wang ◽  
Xiaoyu Zhao ◽  
Jieyu Song ◽  
Jing Wu ◽  
Yuqi Zhu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Inactivated Vaccine ◽  
Protein Subunit ◽  
The Third ◽  
Vaccine Booster ◽  
Push Forward ◽  
Rapid Transmission

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

scholarly journals Comparative trials of live attenuated and detergent split influenza virus vaccines

1975 ◽  
Vol 75 (3) ◽  
pp. 425-444 ◽  
Author(s):  
J. S. Mackenzie ◽  
Isobel Mackenzie ◽  
Julie Lloyd ◽  
Veronica Dent
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Subunit Vaccine ◽  
Geometric Mean ◽  
Haemagglutination Inhibition ◽  
Neutralizing Antibody ◽  
Saline Control ◽  
Serum Samples ◽  
Live Virus ◽  
Live Virus Vaccine

SUMMARYComparative clinical trials of live attenuated and detergent-split subunit influenza virus vaccines were undertaken with 1048 volunteers in Western Australia. Volunteers were divided into three main groups, each of which received either live virus vaccine or a saline control administered intranasally, or subunit vaccine injected subcutaneously. No differences were recorded between the three groups in their post-vaccination symptoms. Serum samples were collected at various times up to 50 weeks after vaccination, and antibody titres were measured by haemagglutination-inhibition (HI) tests and, for 231 volunteers, by virus neutralization tests. The two vaccines were almost equivalent in inducing seroconversion in vaccinees with pre-trial HI titres of 96 or less, but the subunit vaccine stimulated a higher geometric mean HI antibody titre. The longevity of the HI antibody response was greater for the live virus vaccine. The height of the response and the longevity of neutralizing antibody were the same for both vaccines. Both vaccines provided a high degree of protection against epidemic A/England/42/72 influenza, and some protection against A/Port Chalmers/1/73 influenza.

scholarly journals The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC-COV1901

2021 ◽  
Author(s):  
Szu-Min Hsieh ◽  
Shan-chwen Chang ◽  
Hao-Yuan Cheng ◽  
Shin-Ru Shih ◽  
Chia En Lien
Keyword(s):  
Clinical Study ◽  
Antibody Titer ◽  
Subunit Vaccine ◽  
Booster Dose ◽  
Phase 1 ◽  
Neutralizing Antibody ◽  
Dose Schedule ◽  
Protein Subunit ◽  
Antibody Persistence

AbstractIn this extension of the phase 1 clinical study, we report the immunogenicity and reactogenicity of the booster dose of a COVID-19 vaccine, MVC-COV1901, administered six months after the completion of the primary two dose schedule. Antibody persistence was detected at 6 months after the second dose of MVC-COV1901, albeit at reduced levels. At 28 days after the booster dose, the neutralizing antibody titer was 1.7-fold higher compared to the previous peak at 2 weeks after the second dose. These data demonstrated the safety and immunogenicity of booster shot of MVC-COV1901 after the primary schedule of the vaccine.

scholarly journals Safety and immunogenicity of a heterologous booster of protein subunit vaccine MVC-COV1901 after two doses of adenoviral vector vaccine AZD1222

2021 ◽  
Author(s):  
Shu-Hsing Cheng ◽  
Yi-Chun Lin ◽  
Cheng-Pin Chen ◽  
Chien-Yu Cheng
Keyword(s):  
Adenoviral Vector ◽  
Subunit Vaccine ◽  
Booster Dose ◽  
Neutralizing Antibody ◽  
Protein Subunit ◽  
Igg Antibody ◽  
Vector Vaccine ◽  
Antibody Titers

We report the interim safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 or 24 weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers were 14- and 8.6-fold increased, respectively, when compared to the titer levels on the day of the booster dose. These interim results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222.

scholarly journals SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Narayanaiah Cheedarla ◽  
Venkata Satish Bollimpelli ◽  
Sailaja Gangadhara ◽  
Venkata Viswanadh Edara ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Significant Loss ◽  
Lung Pathology ◽  
Live Virus ◽  
Suitable Candidate ◽  
Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

scholarly journals A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

2005 ◽  
Vol 86 (5) ◽  
pp. 1435-1440 ◽  
Author(s):  
Milosz Faber ◽  
Elaine W. Lamirande ◽  
Anjeanette Roberts ◽  
Amy B. Rice ◽  
Hilary Koprowski ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Protein S ◽  
S Protein ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune ◽  
Animal Reservoirs ◽  
S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

scholarly journals Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

2021 ◽  
Author(s):  
Noa Eliakim Raz ◽  
Amos Stemmer ◽  
Yaara Leibovici-Weissman ◽  
Asaf Ness ◽  
Muhammad Awwad ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neutralizing Antibodies ◽  
Multivariable Analysis ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Clinical Frailty Scale ◽  
Younger Adults ◽  
The Third ◽  
Antibody Titers ◽  
Level 2

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.

scholarly journals A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates

2021 ◽  
Author(s):  
Neil C Dalvie ◽  
Lisa H Tostanoski ◽  
Sergio A Rodriguez-Aponte ◽  
Kawaljit Kaur ◽  
Sakshi Bajoria ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Subunit Vaccine ◽  
Hepatitis B Surface Antigen ◽  
Low Cost ◽  
Humoral Response ◽  
High Volume ◽  
Developed Countries ◽  
Protein Subunit ◽  
Middle Income

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

scholarly journals Experiments with the soluble antigen of rabies in suckling mouse brains

1957 ◽  
Vol 55 (3) ◽  
pp. 361-373 ◽  
Author(s):  
M. van den Ende ◽  
A. Polson ◽  
G. S. Turner
Keyword(s):  
Rabies Virus ◽  
Neutralizing Antibody ◽  
Financial Assistance ◽  
Experimental Results ◽  
Soluble Antigen ◽  
Infective Virus ◽  
Suckling Mouse ◽  
High Concentration ◽  
Live Virus

A study has been made of the properties of soluble antigen in the brains of infant mice infected intracerebrally with the Flury strain of rabies virus.Soluble antigen is produced at the same time as infective virus, and reaches a high concentration in a period of 2–3 days.It can be partially purified by precipitation at pH 4·3. It is partially resistant to the action of trypsin, RNAse and DNAse. It is relatively stable at pH 6–10.Experimental results suggest that the soluble antigen remains antigenically active after heating at 56° C. and treatment with 0·5% phenol or 0·35% formal-dehyde, but that such heating markedly reduces the ability to stimulate formation of neutralizing antibody.Rabbits and mice appear to differ in the production of neutralizing antibody following immunization against soluble antigen in which residual live virus was inactivated by heat, phenol or formaldehyde.It is suggested that this difference may depend on the different susceptibility to traces of incompletely inactivated virus remaining in the immunizing antigens.The authors are grateful to Miss T. Madsen for her assistance in some aspects of this work. Dr N. Sapeika kindly made available facilities for the in vitro anaphylaxis experiments.Financial assistance was received from the Nkana-Kitwe and Chingola Poliomyelitis Research Funds.

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