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June 1, 2021by Immunise - a PI India InitiativeResources

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

URL

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext

Date of publication

February 19, 2021

Category of vaccine:

Vaccine efficacy

Study Design

Three single-blind randomised controlled trials

Country of Study

UK, Brazil, South Africa

Level of Evidence

Level I: RCT

Aim/ Question studied

The pooled analysis of ChAdOx1 nCoV-19 trials and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses Furthermore, demonstrate the immunogenicity and protection afforded by the first dose prior to the administration of a booster dose.

Study done / What did they do?

Across the four studies, 24 422 people were recruited and vaccinated, with 17 178 of them included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine).

COV001 (UK) recruited healthy adults aged 18–55. COV002 (UK) and COV003 (Brazil) enrolled adults aged 18 and up, with a focus on health-care workers and others at high risk of SARS-CoV-2 infection. COV005 (South Africa) enrolled adults between the ages of 18 and 65.

All participants who were SARS-CoV-2 N protein seronegative at baseline had at least 14 days of follow-up after the second dose and had no evidence of previous SARS-CoV-2 infection from NAAT swabs were included in the primary analysis. All participants who received at least one dose were evaluated for safety.

Results

Exploratory analyses revealed that vaccine efficacy after a single standard dose of vaccine was 76.0 % from day 22 to day 90 after vaccination.

After the second dose, efficacy was higher in participants with a longer prime-boost interval (vaccine efficacy 81.3 % [95 % CI 60.3–91.2] at 12 weeks) than in those with a short interval (vaccine efficacy 55.1 %[33.0–69.9] at <6 weeks). These findings are supported by immunogenicity data, which show that binding antibody responses are more than two-fold higher after a 12-week interval compared to a 6-week interval in people aged 18–55.

Conclusion

The findings of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with the findings of the trials’ interim analysis, confirming that the vaccine is effective, with results varying by dose interval in exploratory analyses. A 3-month dose interval may have advantages over a programme with a short dose interval for rolling out a pandemic vaccine to protect the greatest number of people as soon as possible when supplies are scarce, while also improving protection after receiving a second dose.

Summary

The ChAdOx1 nCoV-19 (AZD1222) vaccine was approved for emergency use in the UK based on interim efficacy results from 131 cases of primary symptomatic COVID-19, with efficacy based on two of the vaccine’s four trials. In the UK the vaccine will be administered in two doses, 12 weeks apart.

After another month of data collection, this report provides updated primary efficacy results. Efficacy estimates now include data from all four vaccine studies from three countries, whereas the interim analysis only included data from two studies in efficacy assessments due to the small number of cases in the smaller studies.

The primary analysis backs up the interim analysis’s findings that the vaccine is effective and safe. Exploratory analyses show that a longer prime-boost interval results in higher vaccine efficacy and that a single dose of vaccine is effective in the first 90 days, providing additional evidence for current policy.

June 1, 2021by Immunise - a PI India InitiativeResources

Safety and efficacy of a rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia

To report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial.

URL	https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext
Date of publication	February 02, 2021
Category:	Vaccine Efficacy Vaccine Safety
Study Design	Randomised controlled phase 3 trial
Country of Study	Moscow, Russia
Level of Evidence	Level I : RCT
Aim/ Question studied	To report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial.
Study done / What did they do?	The researchers in this study present the preliminary clinical efficacy results of the rAd26 and rAd5 vector-based COVID-19 vaccine Gam-COVID-Vac in a randomised, double-blind, placebo-controlled multicentre phase 3 trial in Moscow, Russia, with 21 862 participants. They present the trial’s initial immunogenicity findings, which include receptor-binding domain-specific IgG titers, virus neutralising antibody titers, and IFN- response.
Results	The phase 3 trial of Gam-COVID-Vac showed efficacy 91·6% against COVID-19 and was well tolerated in a large cohort, according to the interim analysis.
Conclusion	The interim analysis of the randomised, controlled, phase 3 trial of Gam-COVID Vac in Russia revealed high efficacy, immunogenicity, and a good tolerability profile in participants aged 18 years of age or older
Summary	Gam-COVID-Vac (Sputnik V), a heterologous recombinant adenovirus (rAd)-based vaccine, demonstrated good safety and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. The researchers present preliminary findings from the interim analysis of this phase 3 trial on the efficacy and safety of Gam-COVID-Vac.

June 1, 2021by Immunise - a PI India InitiativeResources

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial

They presented preliminary findings from a phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose administered on day 28.

URL	https://www.sciencedirect.com/science/article/pii/S1473309921000700
Date of publication	8 March 2021, The Lancet Infectious Disease
Category:	Vaccine Safety
Study Design	Double-blind, randomised control trial (RCT)
Country of Study	India
Level of Evidence	LEVEL I: RCT
Aim/ Question studied	They presented preliminary findings from a phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose administered on day 28.
Study done / What did they do?	At nine hospitals in India, the researchers conducted a double-blind, randomised, multicentre, phase 2 clinical trial to assess the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12–65 years). They present preliminary results of immunogenicity and safety studies on BBV152 in 380 vaccinated adults and adolescents. BBV152 stimulated immune responses and induced Th1-biased T-cell responses.
Results	The 3-month post-second-dose GMTs (MNT50) in the phase 1 trial were 39.9 (95% CI 32·0–49·9) in the 3g with Algel-IMDG group, 69.5 in the 6 g with Algel group, 53.3 in the 6 g with Algel group, and 20.7 in the Algel alone group.
Conclusion	BBV152 ( Covaxin) induced high neutralising antibody responses in the phase 1 trial, which remained elevated 3 months after the second vaccination in all participants. In the phase 2 trial, BBV152 demonstrated improved reactogenicity and safety outcomes, as well as improved humoral and cell-mediated immune responses when compared to the phase 1 trial. The 6 g formulation with Algel-IMDG has been chosen for the phase 3 efficacy trial.
Summary	BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 g or 6 g) formulated with an alum-adsorbed toll-like receptor 7/8 agonist molecule (IMDG) (Algel). BBV152 induced high neutralising antibody responses in the phase 1 trial, which remained elevated 3 months after the second vaccination in all participants. In comparison to the phase 1 trial, BBV152 demonstrated improved reactogenicity and safety outcomes, as well as enhanced humoral and cell-mediated immune responses in the phase 2 trial. The 6 g formulation with Algel-IMDG has been chosen for the phase 3 efficacy trial. Overall participant retention rates in the 3 g with Algel-IMDG group were 97%, and in the 6 g with Algel-IMDG group were 93 %.

June 1, 2021by Immunise - a PI India InitiativeResources

COVID-19 optimal vaccination policies: A modeling study on efficacy, natural and vaccine-induced immunity responses

The goal of the study is to compare different vaccine profiles in order to compute optimal COVID-19 vaccination policies and to assess the impact of hypothetical reinfection and immunisation responses. According to the study simulations, the optimal strategy design is influenced by vaccine profile and natural immunity period. Similarly, the researchers believe that both natural and vaccine-induced immunity will be critical in lowering COVID-19 disease mortality and prevalence levels.

URL	https://www.sciencedirect.com/science/article/pii/S0025556421000596?via%3Dihub
Date of publication	4 May 2021, Mathematical Biosciences
Category :	Vaccine Efficacy Vaccine-induced immunity
Study Design	Mathematical Model- classical Kermack–McKendrick model.
Country of Study	Mexico
Level of Evidence	Economic study / Decision analyses: Systematic review of Level-I studies.
Aim/ Question studied	The main objective is the formulation of optimal schedules for vaccine administration that ensure: 1.To cover a target population fraction in a fixed time horizon. 2.To minimize COVID-19 burden quantified in Disability-Adjusted Life Years (DALYs). 3. To preserve hospitalization occupancy below a required bound.
Study done / What did they do?	The goal of the study is to compare different vaccine profiles in order to compute optimal COVID-19 vaccination policies and to assess the impact of hypothetical reinfection and immunisation responses. According to the study simulations, the optimal strategy design is influenced by vaccine profile and natural immunity period. Similarly, the researchers believe that both natural and vaccine-induced immunity will be critical in lowering COVID-19 disease mortality and prevalence levels.
Results	In SCN-1: They observe CP (counter vaccine policy) and OVP reduce the symptomatic prevalence and cumulative deaths. SCN-2: 50% coverage at a time horizon of 1 year, displays an improvement from 1.5 to 3 times regarding the counterfactual scenariofor the cumulative deaths at time horizon. Also, there is a notorious im-provement in the hospital occupancy. SCN-3: There has been a significant reduction in the prevalence and total number of deaths associated with the uncontrolled outbreak. This decrease corresponds to the vaccine reproductive number values associated with each vaccine-induced immunity. SCN-4:After a year of natural immunity, the burden of COVID-19 drops to around 120 DALYs.
Conclusion	The researchers correlate vaccination rate with available vaccine stock and health system response—which is constrained by logistics, management, politics, and other issues associated with each vaccine development. As a result, their research contribution can assist decision-makers in developing vaccination schedules for homogeneous populations.
Summary	This study emphasises the significance of knowing the vaccine profile as well as the natural immunity period when developing an optimal vaccination strategy. The simulation is run against various vaccine-induced and natural immunisation profiles, allowing the effects of these variables to be studied and optimal dose administration schedules to be developed. Furthermore, the optimal solution meets modelling constraints in order to achieve the desired vaccination coverage while avoiding healthcare system overload. The researchers optimised vaccination strategies by reducing the COVID-19 burden, which was measured in DALYs. They use an optimal control approach to answer WHO-SAGE vaccination modelling questions.

June 1, 2021by Immunise - a PI India InitiativeResources

Public health impact of delaying the second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent-based modeling study

To estimate the population health outcomes of SARS-CoV-2 mRNA vaccination with a delayed second dose versus a standard schedule.

URL	https://www.bmj.com/content/373/bmj.n1087
Date of publication	12 May 2021,BMJ
Category :	Vaccine effectiveness
Study Design	Agent based modeling study.
Country of Study	US
Level of Evidence	Level-I studies
Aim/ Question studied	To estimate the population health outcomes of SARS-CoV-2 mRNA vaccination with a delayed second dose versus a standard schedule.
Study done / What did they do?	This study uses agent-based modelling to compare the impact of delayed second dose vaccine policies on infections, hospitalizations, and mortality to the current on-schedule two-dose regimen. To account for uncertainty, they used sensitivity analysis and looked at a variety of different scenarios, such as whether the vaccine provides sterilising immunity or only symptomatic immunity. They also looked at a new dosing strategy in which a delayed second dosage regimen is used for people under the age of 65, but not before fully vaccinating older people.
Results	The delayed second dose strategy was optimal for vaccine efficacies of at least 80% and vaccination rates of at least 0.3% of the population per day.
Conclusion	A delayed second dose vaccination strategy, at least for people under the age of 65, could result in lower cumulative mortality.
Summary	The study’s aim is to compare the population health outcomes of a delayed second dose of SARS-CoV-2 mRNA vaccination to the standard schedule. Delaying the second dose could result in up to 20% lower mortality for vaccination rates of 0.1% to 0.3 % of the population per day and one-dose vaccine efficacy of 80% or higher. Delaying the second dose, but prioritizing it for people aged ≥65 can result in lower mortality rates compared to the standard two-dose strategy, even at vaccination rates of up to 1% of the population per day. According to recent calculations, the efficacy of the first dose for the Pfizer and Moderna vaccines is 92.6 % and 92.1 %, respectively, while the CDC estimates a single-dose vaccine efficacy of 80 %. This is greater than the efficacy of Johnson & Johnson’s one-dose regimen, which is estimated to be 66%. Considering the high first-dose efficacy of the BNT162b2 and mRNA-1273 vaccines, some authors have proposed a delayed second dose strategy in the hopes of increasing vaccination rates and lowering cumulative mortality.

June 1, 2021by Immunise - a PI India InitiativeResources

The emergence of new strains of SARS-CoV-2. What does it mean for COVID-19 vaccines

This experts review article is based on various studies on the effectiveness of existing covid vaccines against new strains.

URL	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074646/
Date of publication	April 25, 2021,NIH
Category:	Vaccine Effectiveness
Study Design
Country of Study
Level of Evidence	Level V Therapeutic studies: Expert Review
Aim/ Question studied	This experts review article is based on various studies on the effectiveness of existing covid vaccines against new strains.
Study done / What did they do?
Results
Conclusion
Summary	Brazilian P.1, UK B.1.1.7, and South African 1.351 mutations are dangerous because they avoid detection by the immune system, bind strongly to the ACE2 receptor, and may cause additional harm. In a nutshell, an expert review based on research on various vaccines against new strains was conducted, and the findings revealed that BioNTech-Pfizer was effective against Brazil strains but slightly less effective against the UK and African strains. Astra Zeneca-University of Oxford was effective against strains from the United Kingdom and Brazil, but not those from South Africa. Against the UK strain, both the Indian vaccine (Covaxin) and the Moderna vaccine (mRNA-1273) were effective. There is no specific data available for Brazil, South Africa, New York, and California strain. In contrast, the Johnson & Johnson Vaccine (Ad26.COV2.S) is effective against variants found in the United Kingdom, Brazil, and South Africa.

June 1, 2021by Immunise - a PI India InitiativeResources

Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study.

The aim was to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer.

URL	https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00213-8/fulltext
Date of publication	April 27, 2021, The Lancet Oncology
Category of vaccine:	Vaccine Safety
Study Design	prospective cohort study
Country of Study	London, UK
Level of Evidence	Level IV: cohort study
Aim/ Question studied	The aim was to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer.
Study done / What did they do?	They included patients with cancer and healthy controls (mostly health-care workers) from three London hospitals in this prospective longitudinal observational study to allow for comparisons of vaccine immunogenicity and safety. Participants were eligible for the BNT162b2 vaccine, were screened, and were approached to participate in the SOAP-02 study
Results	One dose of the BNT162b2 vaccine is ineffective in cancer patients. Immunogenicity significantly increased in patients with solid cancer within 2 weeks of a vaccine boost on day 21 after the first dose. These findings support the prioritisation of cancer patients for an early (day 21) second dose of the BNT162b2 vaccine.
Conclusion	The low vaccine efficacy reported for cancer patients receiving seasonal vaccines, and imply that single-dose BNT162b2 vaccination leaves most cancer patients immunologically unprotected.
Summary	The objective of this prospective observational study was to evaluate the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in cancer patients. They included 151 patients with solid and hematological cancers, providing the first insights into the antibody and T-cell responses to the mRNA-based SARS-CoV-2 BNT162b2 vaccine, as well as its safety in an immunocompromised patient population, to our knowledge. Furthermore, they assess the impact of different dosing schedules in this population. One 30 g dose of the BNT162b2 vaccine yields poor efficacy in cancer patients, as measured by seroconversion rates, viral neutralisation capacity, and T-cell responses at 3 and 5 weeks after the first inoculum. Immunogenicity significantly increased in patients with solid cancer within 2 weeks of a vaccine boost on day 21 after the first dose.

June 1, 2021by Immunise - a PI India InitiativeResources

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

To compare rates of cardiovascular and haemostatic events in Denmark and Norway in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S to rates observed in the general population.

URL	https://www.bmj.com/content/373/bmj.n1114
Date of publication	05 May 2021,BMJ
Category:	Vaccination side effects
Study Design	Population based cohort study
Country of Study	Denmark and Norway
Level of Evidence	Level IV: cohort study
Aim/ Question studied	To compare rates of cardiovascular and haemostatic events in Denmark and Norway in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S to rates observed in the general population.
Study done / What did they do?	In this large binational cohort study, They observed 28-day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people were compared to expected rates based on national age and sex specific background rates from the two countries’ general populations.
Results	The standardised morbidity ratio for arterial events was 0.97 among 281 264 people who received ChAdOx1-S, and 59 venous thromboembolic events were observed in the vaccinated cohort compared to 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 and 11 excess events per 100 000 vaccinations. The rate of cerebral venous thrombosis was higher than expected.
Conclusion	Among recipients of ChAdOx1-S, the absolute risks of venous thromboembolic events were low. The results of the safety outcomes were mostly reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding.
Summary	This cohort study, which was conducted among 18-65-year-olds, found that increased rates of venous thromboembolism were observed within 28 days of ChAdOx1-S vaccination in Denmark and Norway, corresponding to 11 excess events per 100 000 vaccinations, including 2.5 excess cerebral venous thrombosis events per 100 000 vaccinations. Furthermore, the vaccinated group had slightly higher rates of thrombocytopenia, coagulation disorders, and bleeding. As a result, the absolute risks described in this study are small in light of the proven benefits of covid-19 vaccination and the globally high incidence of SARS-CoV-2 infection.

June 1, 2021by Immunise - a PI India InitiativeResources

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: a test-negative case-control study

To estimate the effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths.

URL	https://www.bmj.com/content/373/bmj.n1088.full
Date of publication	13 May 2021, BMJ
Category	Vaccine Effectiveness
Study Design	Test negative case-control study
Country of Study	England
Level of Evidence	Level IV: case-control study
Aim/ Question studied	To estimate the effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths.
Study done / What did they do?	In the test-negative case control study, they included 156 930 adults aged 70 years and older who reported symptoms of covid-19. This study provides preliminary real-world evidence for the efficacy of the Pfizer-BioNTech BNT162b2 and Oxford-Asta-Zeneca ChAdOx1-S vaccines against symptomatic covid-19, hospitalizations, and death in older people in England.
Results	Participants aged 80 years and older who received BNT162b2 vaccination before January 4, 2021 had a higher risk of testing positive for covid-19 in the first nine days after vaccination. Vaccine effects were observed 10 to 13 days after vaccination, yielding a vaccine effectiveness of 70%. Vaccination effectiveness of 89 % 14 days after the second dose. The vaccine’s effectiveness with BNT162b2 was 61%. With ChAdOx1-S, effects were seen 14 to 20 days after vaccination, with an effectiveness of 60% from 28 to 34 days, increasing to 73% from day 35 onwards.
Conclusion	-Vaccination with either BNT162b2 or ChAdOx1-S resulted in a significant reduction in symptomatic covid-19 in older adults, as well as additional protection against severe disease.
Summary	-A single dose of either BNT162b2 or ChAdOx1-S provides significant protection against covid-19 as well as additional protection against severe disease for at least six weeks, including protection against the UK variant of concern (B.1.1.7) – A single dose of either vaccine provides 60-70% protection against symptomatic covid-19 and approximately 80 % protection against hospitalisation. In adults aged 70 and up, BNT162b2 and ChAdOx1-S provide comparable levels of protection.

June 1, 2021by Immunise - a PI India InitiativeResources

Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women

To assess the immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women, including the ability to protect against emerging SARS-CoV-2 variants of concern.

URL	https://jamanetwork.com/journals/jama/fullarticle/2780202
Date of publication	May 13, 2021,Jama
Category:	Vaccine safety
Study Design	prospective cohort study
Country of Study
Level of Evidence	Level IV: exploratory, descriptive, prospective cohort study.
Aim/ Question studied	To assess the immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women, including the ability to protect against emerging SARS-CoV-2 variants of concern.
Study done / What did they do?	An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine, 28 women who had confirmed SARS-CoV-2 infection, his study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.
Results	COVID-19 mRNA vaccines were immunogenic, as quantified by both humoral and cellular immune responses, in pregnant, lactating, and nonpregnant, nonlactating women. Following the second dose of the mRNA vaccines, 14% of pregnant women,lactating women 44% and 52% of nonpregnant women reported fever. Antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses against viral variants were preserved.
Conclusion	Immunogenicity was demonstrated in all cases, and antibodies elicited by the vaccine were found in infant cord blood and breast milk. Vaccinated women, both pregnant and nonpregnant, developed cross-reactive immune responses against SARS-CoV-2 variants of concern.
Summary	This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. As a result, data on vaccine safety and immunogenicity in these populations is scarce. The goal To test the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including the ability to protect against emerging SARS-CoV-2 variants of concern. COVID-19 mRNA vaccines shows both humoral and cellular immune responses, in pregnant, lactating, and nonpregnant, nonlactating women. In a small convenience sample, COVID-19 mRNA vaccines were immunogenic in pregnant and lactating women and induced immune responses against SARS-CoV-2 variants. This study validates that vaccination elicits higher antibody responses than does infection.