Seasonal influenza vaccines offer little protection against pandemic influenza virus strains. It is difficult to create effective prepandemic vaccines because it is uncertain which influenza virus subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)–lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and influenza B virus lineages. This multivalent vaccine elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched viral strains, and this protection was at least partially dependent on antibodies. Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens. Description A cornucopia of antigens Vaccines serve as an indispensable tool for the control and prevention of influenza, but several challenges remain. Some populations, for example, the elderly, respond poorly to vaccination. Furthermore, the highly variable nature of influenza viruses can make targeting optimal antigens difficult. Broadly neutralizing antibodies have been proposed as a solution to such disadvantages, but they present their own pitfalls, including limited cross-reactivity to both influenza A and B strains and the need for repeated injections during flu season. Arevalo et al. developed a nucleoside-modified messenger RNA-lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A and B virus subtypes (see the Perspective by Kelvin and Falzarano). Such vaccines may provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens. —STS mRNA vaccines expressing antigens from all known influenza subtypes elicit protective responses in mice and ferrets.

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against coronavirus disease 2019 (COVID-19). This immunity may further be shaped by cross-reactivity with common cold coronaviruses. Mutations arising in S that are associated with altered intrinsic virus properties and immune escape result in the continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will be required to protect against future variants of concern, as for influenza. To offer potent protection against future variants, these second-generation vaccines may need to redirect immunity to epitopes associated with immune escape and not merely boost immunity toward conserved domains in preimmune individuals. For influenza, efficacy of repeated vaccination is hampered by original antigenic sin, an attribute of immune memory that leads to greater induction of antibodies specific to the first-encountered variant of an immunogen compared with subsequent variants. In this Review, recent findings on original antigenic sin are discussed in the context of SARS-CoV-2 evolution. Unanswered questions and future directions are highlighted, with an emphasis on the impact on disease outcome and vaccine design. 

/pdf/impact-of-antigenic-evolution-and-original-antigenic-sin-on-1ymqslae.pdf

Impact of antigenic evolution and original antigenic sin on SARS-CoV-2 immunity

We are currently approaching three years since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 has caused extensive disruptions in everyday life, public health, and the global economy. Thus far, the vaccine has worked better than expected against the virus. During the pandemic, we experienced several things, such as the virus and its pathogenesis, clinical manifestations, and treatments; emerging variants; different vaccines; and the vaccine development processes. This review describes how each vaccine has been developed and approved with the help of modern technology. We also discuss critical milestones during the vaccine development process. Several lessons were learned from different countries during the two years of vaccine research, development, clinical trials, and vaccination. The lessons learned during the vaccine development process will help to fight the next pandemic.

/pdf/sars-cov-2-vaccines-vaccine-development-technologies-and-604ac69z.pdf

SARS-CoV-2 Vaccines, Vaccine Development Technologies, and Significant Efforts in Vaccine Development during the Pandemic: The Lessons Learned Might Help to Fight against the Next Pandemic

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.

/pdf/evolution-of-sars-cov-2-variants-implications-on-immune-1xavlotm.pdf

Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies

http://www.cell.com/article/S2211124722007550/pdf

Emerging viruses: Cross-species transmission of coronaviruses, filoviruses, henipaviruses, and rotaviruses from bats

The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. ABSTRACT The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. Although data on the effectiveness of the primary regimen against omicron (B.1.1.529) are limited, booster programs using mRNA vaccines have been shown to restore protection against infection and symptomatic disease (regardless of the vaccine used for the primary regimen) and maintain high effectiveness against hospitalization. However, effectiveness against infection and symptomatic disease wanes with time after the booster dose. Studies have demonstrated reductions of varying magnitude in neutralizing activity of vaccine-elicited antibodies against a range of SARS-CoV-2 variants, with the omicron variant in particular exhibiting partial immune escape. However, evidence suggests that T-cell responses are preserved across vaccine platforms, regardless of variant of concern. Nevertheless, various mitigation strategies are under investigation to address the potential for reduced efficacy or effectiveness against current and future SARS-CoV-2 variants, including modification of vaccines for certain variants (including omicron), multivalent vaccine formulations, and different delivery mechanisms.

/pdf/the-impact-of-evolving-sars-cov-2-mutations-and-variants-on-11z70jvx.pdf

The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines

ABSTRACT Introduction The coronavirus 19 (COVID-19) pandemic triggered a simultaneous global demand for preventative vaccines, which quickly became a high priority among governments as well as academia and the pharmaceutical industry. Within less than a year after COVID-19 was declared a pandemic, vaccines had received emergency approvals and vaccination campaigns were initiated. Areas covered We discuss the several factors that led to the unprecedented, accelerated development and approval of COVID-19 vaccines, which includes optimization of processes by regulatory authorities, redesign of sequential development processes, learnings from previous pandemics, and prior development of novel vaccine platforms. Expert Opinion Despite unanticipated and complex challenges presented by real-time vaccine development in the context of the evolving COVID-19 pandemic and subsequent ever-changing landscape of public health measures and recommendations, important milestones were reached within extraordinarily short periods and, following roll-out to billions worldwide, the approved vaccines have proven to be well tolerated and effective. Whilst this is an exceptional feat and an example of what can be achieved with collaboration and innovation, there are lessons that can still be learned, including the need for further harmonization between regulatory authorities, modes to react to the pandemic’s ever-evolving challenges, and ensuring equitable vaccine access among low-income countries.

Clinical development and approval of COVID-19 vaccines

Immunization programmes have been globally recognized as one of the most successful medical interventions against infectious diseases. Despite the proven efficacy and safety profiles of coronavirus disease 2019 (COVID-19) vaccines, there are still a substantial number of people who express vaccine hesitancy. Factors that influence vaccine decision-making are heterogenous, complex, and context specific and may be caused or amplified by uncontrolled online information or misinformation. With respect to COVID-19, the recent emergence of novel variants of concern that give rise to milder disease also drives vaccine hesitancy. Healthcare professionals remain one of the most trusted groups to advise and provide information to those ambivalent about COVID-19 vaccination and should be equipped with adequate resources and information as well as practical guidance to empower them to effectively discuss concerns. This article seeks to summarize the currently available information to address the most common concerns regarding COVID-19 vaccination.

/pdf/addressing-covid-19-vaccine-hesitancy-2sm0sd0i.pdf

Addressing COVID-19 vaccine hesitancy

INTRODUCTION
The Omicron BA.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent sub-lineages exhibit partial escape from neutralizing antibodies elicited by vaccines containing or encoding wild-type spike protein. In response to the emergence of Omicron sub-lineages, variant-adapted vaccines that contain or encode for Omicron spike protein components have been developed.


AREAS COVERED
This review presents currently available clinical immunogenicity and safety data on Omicron variant-adapted versions of the BNT162b2 messenger RNA (mRNA) vaccine and summarizes the expected mechanism of action, and rationale for development, of these vaccines. In addition, challenges encountered during development and regulatory approval are discussed.


EXPERT OPINION
Omicron-adapted BNT162b2 vaccines provide a wider breadth and potentially more durable protection against Omicron sub-lineages and antigenically aligned variants when compared with the original vaccine. As SARS-CoV-2 continues to evolve, further vaccine updates may be required. To facilitate this, a globally harmonized regulatory process for the transition to updated vaccines is needed. Next-generation vaccine approaches may provide broader protection against future variants.

https://www.tandfonline.com/doi/pdf/10.1080/14760584.2023.2232851?needAccess=true&role=button

Clinical development of variant-adapted BNT162b2 COVID-19 vaccines: the early Omicron era.

Although pediatric populations experienced lower COVID-19 severity and mortality than adults, the epidemiology of this disease continues to evolve. COVID-19 clinical manifestations in pediatrics commonly include fever and cough, but may differ from adults and by variant. Serious complications, including MIS-C, rarely occur. Although early data showed a decreased likelihood of COVID-19 transmission from children versus adults, outbreaks and viral shedding studies support pediatric transmission potential. Children may mount more robust initial immune responses to SARS-CoV-2 versus adults. COVID-19 vaccines with available pediatric data include BNT162b2, mRNA-1273, CoronaVac, and BBIBP-CorV. Depending on age group and jurisdiction, BNT162b2 and mRNA-1273 have received full approval or emergency/conditional authorization in the United States and European Union from 6 months of age. Clinical trials have shown BNT162b2 and mRNA-1273 safety and high efficacy in pediatric populations, with demonstrably noninferior immune responses versus young adults. Real-world studies further support BNT162b2 safety and effectiveness against the Delta variant. mRNA vaccination benefits are considered to outweigh risks, including myocarditis; however, pediatric vaccination rates remain relatively low. Given a growing body of clinical trial and real-world data showing vaccine safety and effectiveness, pediatric vaccination should be prioritized as an important strategy to control the pandemic.

/pdf/covid-19-epidemiology-immunity-and-vaccine-development-in-1dyi0g8y.pdf

COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review

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