Capsule Summary
m-RNA Vaccines for COVID-19, a short review
COVID-19, also known as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic starting in late 2019. COVID-19 has affected more than 200 million people worldwide leading to greater than 4 million deaths, and this severe respiratory disease continues to threaten public health and safety on a massive scale. In the absence of definitive therapeutics to treat COVID-19, vaccines represent the major preventative strategy to protect human lives. Vaccines have helped us defeat numerous life-threatening infectious diseases, and the emerging novel vaccines for COVID-19 represent our best hope to not only protect human lives but also lessen the impact on limited public health resources worldwide. Vaccines train our immune cells to generate protective antibodies against invading pathogens, thereby strengthening out body’s defense system against infectious diseases.
One of the earliest breakthroughs in COVID-19 vaccines came with the development of novel messenger RNA (mRNA) based vaccines, which showcases a paradigm shift in the vaccine field. mRNA vaccines are designed to encode a specific structural component of the invading pathogen [1-3]. Upon injection of the mRNA vaccine, our immune cells use that genetic code to generate pathogen specific proteins. These newly generated proteins are recognized by our immune cells as foreign antigens, leading to a robust immune response and production of protective antibodies. Importantly, the injected mRNA has a short lifespan within human tissues and is effectively destroyed by our cells without any adverse consequences on our genetic makeup [3, 4]. Generation of protective antibodies helps defend our bodies against subsequent exposure to the actual infection causing pathogen.
The COVID-19 mRNA vaccine encodes the genetic code for its spike protein, which helps viral attachment to our cells aiding its intracellular entry [3]. mRNA vaccines utilizes a lipid-nanoparticle based delivery system which shield the mRNA from degradation and allows for efficient delivery of the mRNA inside our immune cells [3]. mRNA based COVID-19 vaccines approved for human use via the emergency use authorization are currently exclusively being manufactured by the two major pharmaceutical companies including Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273).
The current full vaccination schedule for these vaccines dictate two doses administered at least 21 days apart. Vaccination with two doses of Pfizer-BioNTech and Moderna vaccine provides an overall effectiveness of approximately 95.3% and 94.1% respectively against COVID-19 illness including severe disease [5, 6]. However, the need for cold-chain storage for these mRNA vaccines introduces logistical difficulties in handling, especially for developing countries. From a safety standpoint, mRNA vaccines are relatively safe, with low incidence of minor to moderate adverse events observed in clinical trials. Anaphylactic reactions have been documented at rates of 4.7 cases per million doses of Pfizer-BioNTech vaccine and 2.5 cases per million of Moderna vaccine [7]. However, scientists believe and attribute these allergic response to the pre-existing antibodies against the PEGylated lipids used in delivery formulation of the mRNA vaccines [3].
Nonetheless, scientists are to be commended for developing these mRNA based vaccines against COVID-19 in such a short time span, which is not less than a miracle. The significant protection offered by these vaccines against preventing severe COVD-19 illness has had a tremendous impact on our everyday lives. With the emergence of increasingly transmissible variants of COVID-19, the mRNA-based vaccines could be adapted to deliver the genetic codes against specific viral variants. mRNA-based vaccine platform provides an excellent mechanism for developing novel vaccines against COVID-19 and will continue to play a pivotal role in our fight against life-threatening infectious diseases.
Information Source:
1. Pardi, N., et al., mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov, 2018. 17(4): p. 261-279.
2. Van Lint, S., et al., mRNA: From a chemical blueprint for protein production to an off-the-shelf therapeutic. Hum Vaccin Immunother, 2013. 9(2): p. 265-74
3. Chaudhary, N., D. Weissman, and K.A. Whitehead, mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat Rev Drug Discov, 2021
4. Schlake, T., et al., Developing mRNA-vaccine technologies. RNA Biol, 2012. 9(11): p. 1319-30.
5. Haas, E.J., et al., Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet, 2021. 397(10287): p. 1819-1829
6. Baden, L.R., et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med, 2021. 384(5): p. 403-416.
7. Shimabukuro, T.T., M. Cole, and J.R. Su, Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US-December 14, 2020-January 18, 2021. JAMA, 2021. 325(11): p. 1101-1102.
Disclaimer
The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.
Copyright Reserved @2021
independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Capsule Summary
Encouraging Safety and Efficacy Data of the COVID-19 vaccine NVX-CoV2373 manufactured by Novovax from the United States and Mexico Trial
NVX-CoV2373 manufactured by Novovax is a protein-based vaccine, which offers protection against SARS-COV2 infection. It contains the spike protein of the coronavirus, which is formulated as a nanoparticle.
Study Methodology
This was a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021. This trial was designed to assess the efficacy and safety of NVX-CoV2373 in patients who are at least 18 years or above and did not have acute SARS-Cov2 infection earlier.
Study Participants were randomly assigned in a 2:1 ratio to receive 2 doses of either NVX-CoV2373 or placebo 21 days apart.
Primary Objective
This was a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021. This trial was designed to assess the efficacy and safety of NVX-CoV2373 in patients who are at least 18 years or above and did not have acute SARS-Cov2 infection earlier.
Study Participants were randomly assigned in a 2:1 ratio to receive 2 doses of either NVX-CoV2373 or placebo 21 days apart.
Results
29,582 study participants (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,174 received vaccine while 9868 received placebo.
Efficacy Data
Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest — largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7).
Solicited local and systemic adverse events were predominantly mild to moderate and transient and occurred more frequently among NVX-CoV2373 recipients compared to placebo.
Conclusion
NVX-CoV2373 was safe and effective for the prevention of Covid-19. It has extended stability and easy storage requirements (up to 6 months at refrigerator temperatures), which make it very well suited for global, use.
References
1. https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html Accessed on 16th December 2021.
Information Source: Dunkle, L. M., Kotloff, K. L., Gay, C. L., Áñez, G., Adelglass, J. M., Barrat Hernández, A. Q., Harper, W. L., Duncanson, D. M., McArthur, M. A., Florescu, D. F., McClelland, R. S., Garcia-Fragoso, V., Riesenberg, R. A., Musante, D. B., Fried, D. L., Safirstein, B. E., McKenzie, M., Jeanfreau, R. J., Kingsley, J. K., … Dubovsky, F. (2021). Efficacy and safety of NVX-cov2373 in adults in the United States and Mexico. New England Journal of Medicine.https://doi.org/10.1056/nejmoa2116185
Disclaimer
The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.
Copyright Reserved @2021
independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Capsule Summary
EVUSHELD: Unleashing the power of monoclonal antibodies against COVID-19
The US Food and Drug Administration (FDA) recently granted emergency use authorization (EUA) of EVUSHELD, a monoclonal antibody combination, for the pre-exposure prophylaxis of COVID-19 disease. This EUA represents a paradigm shift in the prevention of a life-threatening disease that has upended our lives for over two years.
EVUSHELD is Authorized for use:
In certain adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms): Who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2. Who have moderate to severe immune-compromised due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination. For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine(s) and/or COVID19 vaccine component(s).
Composition: A combination of MAB’s (Tixagevimab and Cilgavimab)
Manufacturer: Astra Zeneca
Country of Origin: United States of America
Mechanism of Action
Administered as 150 mg of Tixagevimab and 150 mg of Cilgavimab as two separate consecutive intramuscular injections. Harnesses the power of monoclonal antibodies directed against the spike protein of SARS-CoV2. The two antibodies bind to distinct non-overlapping regions of the receptor-binding domain of SARS-CoV2 spike protein. This blocks the interaction of the SARS-CoV2 virus with the human ACE2 receptor, the SARS-CoV2 receptor, which is critical for virus attachment and entry into the cells, thereby ultimately blocking infection. First of its kind monoclonal antibody therapy to prevent COVID-19, potentially providing long-lasting durable protection of up to six months after a single injection.
Clinical Trials
Efficacy data from PROVENT Phase III trial – Pre-exposure prophylaxis (Median follow-up time – 83 days, range 3 to 166 days)
Efficacy data from STORM CHASER Phase III trial – Post-exposure prophylaxis (Median follow-up time – 49 days, range 5 to 115 days)
Conclusion:
Based on these clinical trials, it was concluded that EVUSHELD is effective in reducing the incidence of COVID-19 illness when administered in a Preexposure prophylaxis manner, but not as post-exposure prophylaxis.
Information Source:
Information presented in this article was extracted from a specific EVUSHELD related Factsheet published by the US FDA which can be found at – https://www.fda.gov/media/154701/download
Disclaimer
The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.
Copyright Reserved @2021
independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Capsule Summary
Real world Effectiveness of the Pfizer COVID-19 Vaccine
• A vaccine effectiveness is the measure of how well a vaccine performs in the real world. It is measured by how well the vaccines work to protect communities as a whole (1).
• Vaccine effectiveness is analysed using observational studies where unlike a clinical trial, the participants are not randomly assigned to treatment and a placebo group. A case-control study is commonly used to analyse vaccine effectiveness.
• In a case control study, the vaccination status of the individuals who develop the disease (cases) is compared with the individuals who do not develop the disease (controls) (2).
• A study recently published in the lancet analysed the effectiveness of the BNT162b2 (Pfizer–BioNTech) vaccine in individuals 12 years or older. We have summarized the study findings below. You can access the entire study here .
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02183-8/fulltext
Study Population:
The electronic health records of individuals (≥12 years) who were members of the health-care organization Kaiser Permanente Southern California (CA, USA) were assessed. This study included 3436957 females and 1 637394 males.
Study Endpoints:
BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions was assessed for up to 6 months. The study outcomes included SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions.Effectiveness calculations were based on hazard ratios from adjusted Cox models.
Findings:Study
Reference:
Disclaimer
The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.
Copyright Reserved @2021
independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Capsule Summary
Covaxin Neutralizes SARS-CoV-2 Delta and Omicron variants
Covaxin, also known as BBV152 is an inactivated whole Virion vaccine, developed by Bharat Biotech in collaboration with the Indian Council of Medical Research and National Institute of Virology, India. Previous studies have shown that Covaxin vaccine is 77.8 % efficacious against symptomatic COVID-19 infection and 93.4 % efficacious against severe symptomatic COVID-19 disease in adults [1].
The emergence of new Omicron variant has caused an unprecedented surge in COVID-19 infections worldwide. Omicron variant has more than 30 mutations within the spike protein, and it is causing increased incidence of breakthrough infections in people vaccinated with primary two dose vaccine regimen and boosted individuals [2]. Therefore, it is critical to evaluate the effectiveness of the available vaccines against the Omicron variant.
Objective:
To assess the neutralising activity of sera collected from individuals who received booster dose (6 months after the last dose of primary series) of Covaxin against Omicron variant. (Note: This study is published on the pre-print server medRxiv and has not yet undergone full peer review) [3].
Study Overview:
• Booster dose of Covaxin was administered on Day 215, to individuals who had previously received the primary two dose regimen of Covaxin.
• Sera was collected 28 days after the booster dose.
• Liver Virus Focus Reduction Neutralisation Assay (FRNT) was used to evaluate the neutralising capacity of sera.
Study Results:
Conclusion:
Booster dose of Covaxin induces robust neutralization of the Omicron and Delta variants. Although the study has limitation with respect to small ample size and absence of clinical outcome findings, it does present critical findings in wake of the rampant spread of the Omicron variant.
Information Source:
Edara, V. et al., Covaxin (BB152) Vaccine Neutralizes SARSCoV-2 Delta and Omicron variants. medRxiv preprinthttps://doi.org/10.1101/2022.01.24.22269189,January 28, 2022.
You can access the full article at https://www.medrxiv.org/content/10.1101/2022.01.24.22269189v1.full.pdf
References:
1. Ella, R., et al., Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet, 2021.398(10317): p. 2173-2184.
2. Wang, S.Y., et al., Severe breakthrough COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era. Lancet Microbe, 2022. 3(1): p. e4-e5.
3. Edara, V. et al., Covaxin (BB152) Vaccine Neutralizes SARSCoV-2 Delta and Omicron variants. medRxiv preprint doi:https://doi.org/10.1101/2022.01.24.22269189, January 28, 2022
Disclaimer
The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.
Copyright Reserved @2021
independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Capsule Summary
Pneumococcal Vaccination and Kidney Transplantation
• Patients undergoing kidney transplantation are at a 4-9 times higher risk of developing the invasive pneumococcal disease (IPD) when compared to the general population. (1,2) Immunization can be an important tool which can help protect patients undergoing kidney transplantation from developing IPD.
• The effectiveness of pneumococcal vaccines in patients undergoing solid organ transplantation remains unproven. A recently published study analysed the effects of pneumococcal vaccination on people undergoing kidney transplantation. The study has been summarized below:
Objective:
To analyse if a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) helped to increase the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs).
Study design and Methods:
This was a phase 3, randomized non-blinded trial. 74 KTRs and 65 WLPs were randomized to receive either normal dosage (ND) vaccination (PCV13 (0.5 ml) followed by PPV23 (0.5 ml)) or double dosage (DD) vaccination (PCV13 (1.0 ml) followed by PPV23 (1.0 ml)). Vaccines were given at an interval of 12 weeks.
Primary Endpoint:
Number of participants that reached a protective response five weeks after PPV23 (week 17). A ‘protective response’ was obtained, if the participant had an average pneumococcal antibody geometric mean concentration (GMC) ≥ 1 mg/L
Study Results:
