Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study

http://www.thelancet.com/article/S0140673622000940/pdf

/pdf/the-lancet-commission-on-lessons-for-the-future-from-the-3b11rs1e.pdf

The Lancet Commission on lessons for the future from the COVID-19 pandemic

http://www.thelancet.com/article/S0140673622015859/pdf

Abstract There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT–PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14–30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3–55.7) against confirmed infection and 82.1% (95% CI: 81.4–82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1–36.2) against infection and 72.5% (95% CI: 70.9–74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0−94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1−98.1) 14–30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly. 

/pdf/vaccine-effectiveness-of-heterologous-coronavac-plus-1yzgtsny.pdf

Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil

Introduction The Delta variant of SARS-CoV-2 has caused a new wave of the COVID-19 epidemic in many countries. It is the most infectious variant of SARS-CoV-2 to date, and its high infectivity means that a higher proportion of the population needs to be vaccinated to reduce the disease burden, which poses a substantial public health challenge. Areas covered The evolution of the Delta variant is reviewed, including an overview of the Delta Plus variant with a K417N mutation in the RBD, which may confer an improved immune evasion ability. Decreases in serum neutralizing antibody titers after vaccination against Delta were greater than those against Alpha but less than those against Beta. The protective efficacy of existing vaccines against the Delta variant have declined and is related to the number of doses and the time since vaccination. Expert opinion The currently used vaccines are effective against hospitalization/severe disease due to the Delta variant. Accelerating the popularization of vaccination, improving the coverage rate, and the implementation of intervention measures, such as wearing masks, are effective means to control the spread of the Delta variant and other variants. However, vaccination alone against SARS-CoV-2 without intervention measures may lead to continuous spread and the emergence of new variants.

https://www.tandfonline.com/doi/pdf/10.1080/14760584.2021.1976153

Impact of the Delta variant on vaccine efficacy and response strategies.

Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Our results showed that the humoral and cellular immune responses induced by different vaccines when administered individually differ significantly. In particular, inactivated vaccines showed relatively lower level of neutralizing antibody and T cell responses, but a higher IgG2a/IgG1 ratio compared with other vaccines. Boosting with either recombinant subunit, adenovirus vectored or mRNA vaccine after two-doses of inactivated vaccine further improved both neutralizing antibody and Spike-specific Th1-type T cell responses compared to boosting with a third dose of inactivated vaccine. Our results provide new ideas for prophylactic inoculation strategy of SARS-CoV-2 vaccines.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2021.1957401

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

ABSTRACT Analysis of large-scale gene expression post vaccination can provide an overview of immune responses. We used transcriptional approaches to comprehensively analyze the innate immune response signatures elicited by protein subunit (PS) vaccine ZF2001 and an mRNA vaccine named RRV. A fine-grained time-dependent dissection of large-scale gene expression post immunization revealed that ZF001 induced MHC class II-related genes, including cd74 and H2-Aa, more expeditiously than the RRV. Notably, the RRV induced MHC class I-related genes such as Tap1/2, B2m, and H2-D1/K1. At day 21 post immunization, the titres of binding and neutralization antibody (NAb) induced by both vaccines were comparable, which were accordant with the expression level of genes essential to BCR/TCR signalling transduction and B/T cells activation at day 7. However, compared to ZF2001, the early responses of RRV were more robust, including the activation of pattern recognition receptors (PRRs), expression of genes involved in RNA degradation, and transcription inhibition, which are directly related to anti-viral signals. This pattern also coincided with the induction of cytokines by the RRV. Generally, the transcriptomic patterns of two very different vaccines mapped here provide a framework for establishing correlates between the induction of genes and protection, which can be tailored for evoking specific and potent immune responses against SARS-CoV-2.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2022.2059404?needAccess=true

Transcriptomic analysis of the innate immune signatures of a SARS-CoV-2 protein subunit vaccine ZF2001 and an mRNA vaccine RRV

ABSTRACT Introduction Major emergent infectious diseases (MEID) pose the most serious threat to human health. The research proposes targeted response strategies for the prevention and control of potential MEID. Areas covered Based on the analysis of infectious diseases, this research analyzes pandemics that have a high probability of occurrence and aims to synthesize the past experience and lessons learned of controlling infectious diseases such as coronavirus, influenza, Ebola, etc. In addition, by integrating major infectious disease response guidelines developed by WHO, the European Union, the United States, and the United Kingdom, we intend to bring forward national vaccine R&D development strategies for emergency use. Expert opinion We advise to establish and improve existing laws, regulations, and also prevention and control systems for the emergent R&D and application of vaccines in response to potential infectious diseases. The strategies would not only help increase the various abilities in response to the research, development, evaluation, production, and supervision of emergency vaccines, but also establish surrogate endpoint of immunogenicity protection in early clinical studies to enable a rapid evaluation of the efficacy of emergency vaccines.

https://www.tandfonline.com/doi/pdf/10.1080/14760584.2022.2027240?needAccess=true

The next major emergent infectious disease: reflections on vaccine emergency development strategies

To effectively control and prevent the pandemic of coronavirus disease 2019 (COVID-19), suitable vaccines have been researched and developed rapidly. Currently, 31 COVID-19 vaccines have been approved for emergency use or authorized for conditional marketing, with more than 9.3 billion doses of vaccines being administered globally. However, the continuous emergence of variants with high transmissibility and an ability to escape the immune responses elicited by vaccines poses severe challenges to the effectiveness of approved vaccines. Hundreds of new COVID-19 vaccines based on different technology platforms are in need of a quick evaluation for their efficiencies. Selection and enrollment of a suitable sample of population for conducting these clinical trials is often challenging because the pandemic so widespread and also due to large scale vaccination. To overcome these hurdles, methods of evaluation of vaccine efficiency based on establishment of surrogate endpoints could expedite the further research and development of vaccines. In this review, we have summarized the studies on neutralizing antibody responses and effectiveness of the various COVID-19 vaccines. Using this data we have analyzed the feasibility of establishing surrogate endpoints for evaluating the efficacy of vaccines based on neutralizing antibody titers. The considerations discussed here open up new avenues for devising novel approaches and strategies for the research and develop as well as application of COVID-19 vaccines.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.814365/pdf

Qian Wang

Papers

Impact of the Delta variant on vaccine efficacy and response strategies.

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

Transcriptomic analysis of the innate immune signatures of a SARS-CoV-2 protein subunit vaccine ZF2001 and an mRNA vaccine RRV

The next major emergent infectious disease: reflections on vaccine emergency development strategies

Considerations for the Feasibility of Neutralizing Antibodies as a Surrogate Endpoint for COVID-19 Vaccines