The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

Vaccine perceptions among Black adults with long COVID.

OBJECTIVES: Low uptake of COVID vaccines within Black communities is a concern given the stark racial inequities associated with the pandemic. Prior research details COVID vaccine perceptions within the general population and Black communities specifically. However, Black individuals with long COVID may be more or less receptive to future COVID vaccination than their peers without long COVID. The impact of COVID vaccination on long COVID symptoms is still controversial, since some studies suggest that vaccination can improve long COVID symptoms, whereas other studies report no significant change in symptoms or a worsening of symptoms. In this study, we aimed to characterize the factors influencing perceptions of COVID vaccines among Black adults with long COVID to inform future vaccine-related policies and interventions. DESIGN: We conducted 15 semi-structured, race-concordant interviews over Zoom with adults who reported physical or mental health symptoms that lingered for a month or more after acute COVID infection. We transcribed and anonymized the interviews and implemented inductive, thematic analysis to identify factors influencing COVID vaccine perceptions and the vaccine decision-making process. RESULTS: We identified five themes that influenced vaccine perceptions: (1) Vaccine safety and efficacy; (2) Social implications of vaccination status; (3) Navigating and interpreting vaccine-related information; (4) Possibility of abuse and exploitation by the government and scientific community; and (5) Long COVID status. Safety concerns were amplified by long COVID status and mistrust in social systems due to mistreatment of the Black community. CONCLUSIONS: Among the factors influencing COVID vaccine perceptions, participants reported a desire to avoid reinfection and a negative immune response. As COVID reinfection and long COVID become more common, achieving adequate uptake of COVID vaccines and boosters may require approaches that are tailored in partnership with the long COVID patient community.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Perceptions of Nursing Students' Regarding Coronavirus Vaccination Acceptance: A Mixed Methods Study

Background: The first COVID-19 vaccine was authorized in the United States in December 2020. It is recognized that vaccination is a preventive and effective measure for limiting the coronavirus pandemic. Nursing students' perspectives on vaccine acceptance may be critical for COVID-19 pandemic prevention as future professionals. The study has focused on perceptions of nursing students regarding coronavirus vaccine acceptance.Design: This study was conducted using a sequential explanatory mixed-methods design with two phases. Methods: A convenience sample method was applied in phase one, and 255 nursing school students between February 14 and February 24, 2022, from six universities in Iraq participated. The findings were used in phase two to refine in-depth interview questions that would allow for a deeper investigation of student perceptions. Fifteen participants were questioned one-on-one using personal interviews. Using an inductive method of theme analysis, the dataset was coded, classified, and thematizedResults: Out of 255 students, the results of the quantitative phase revealed that 123 (48.2%), 120 (47.1%), and 12 (4.7%) of them had, respectively, unsound, somewhat sound, and sound perceptions of coronavirus vaccines. Based on the students' perceptions, the main themes from the qualitative phase emerged and include: (persuasion, preservation, accountability, efficacy doubts, and apprehension). Conclusions: Most student nurses have unsound perceptions about COVID-19 vaccinations. Findings showed that nursing students need to take vaccination issues into account and educate others about vaccine production. The development of suitable solutions and interdisciplinary educational programs in the post-pandemic phase may depend on understanding perceptions and encouraging health engagement and awareness. © 2022, Association Res Militaris. All rights reserved.

Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 230 countries and territories worldwide since its outbreak in late 2019. In less than three years, infection by SARS-CoV-2 has resulted in over 600 million cases of COVID-19 and over 6.4 million deaths. Vaccines have been developed with unimaginable speed, and 11 have already been approved by the World Health Organization and given Emergency Use Listing. The administration of several first-generation SARS-CoV-2 vaccines has successfully decelerated the spread of COVID-19 but not stopped it completely. In the ongoing fight against viruses, genetic mutations frequently occur in the viral genome, resulting in a decrease in vaccine-induced antibody neutralization and widespread breakthrough infection. Facing the evolution and uncertainty of SARS-CoV-2 in the future, and the possibility of the spillover of other coronaviruses to humans, the need for vaccines with a broad spectrum of antiviral variants against multiple coronaviruses is recognized. It is imperative to develop a universal coronavirus or pan-coronavirus vaccine or drug to combat the ongoing COVID-19 pandemic as well as to prevent the next coronavirus pandemic. In this review, in addition to summarizing the protective effect of approved vaccines, we systematically summarize current work on the development of vaccines aimed at suppressing multiple SARS-CoV-2 variants of concern as well as multiple coronaviruses.

Immunoinformatics Identification of the Conserved and Cross-Reactive T-Cell Epitopes of SARS-CoV-2 with Human Common Cold Coronaviruses, SARS-CoV, MERS-CoV and Live Attenuated Vaccines Presented by HLA Alleles of Indonesian Population.

Reports on T-cell cross-reactivity against SARS-CoV-2 epitopes in unexposed individuals have been linked with prior exposure to the human common cold coronaviruses (HCCCs). Several studies suggested that cross-reactive T-cells response to live attenuated vaccines (LAVs) such as BCG (Bacillus Calmette-Guérin), OPV (Oral Polio Vaccine), and MMR (measles, mumps, and rubella) can limit the development and severity of COVID-19. This study aims to identify potential cross-reactivity between SARS-CoV-2, HCCCs, and LAVs in the context of T-cell epitopes peptides presented by HLA (Human Leukocyte Antigen) alleles of the Indonesian population. SARS-CoV-2 derived T-cell epitopes were predicted using immunoinformatics tools and assessed for their conservancy, variability, and population coverage. Two fully conserved epitopes with 100% similarity and nine heterologous epitopes with identical T-cell receptor (TCR) contact residues were identified from the ORF1ab fragment of SARS-CoV-2 and all HCCCs. Cross-reactive epitopes from various proteins of SARS-CoV-2 and LAVs were also identified (15 epitopes from BCG, 7 epitopes from MMR, but none from OPV). A majority of the identified epitopes were observed to belong to ORF1ab, further suggesting the vital role of ORF1ab in the coronaviruses family and suggesting it as a candidate for a potential universal coronavirus vaccine that protects against severe disease by inducing cell mediated immunity.

Thermostable vaccines: an innovative concept in vaccine development.

INTRODUCTION: Vaccines represent he most common and safer ways of combating infectious diseases. Loss of potency owing to thermal denaturation or degradation of almost all the vaccines necessitates their storage, transportation, and final dissemination under refrigerated conditions. However, maintenance of a continuous cold chain raises the costs of vaccines significantly. A large number of life-saving vaccines are discarded before their application owing to exposure to sub-optimum temperatures. Therefore, there is a pressing need for the development of a thermostable vaccine with a long shelf life at ambient temperature. AREAS COVERED: A literature search was performed to compile a list of different vaccines, and their storage and handling conditions. Similarly, a separate list was prepared for different coronavirus vaccines. A literature survey was also performed to look at different approaches undertaken globally to address the issue of the cold-chain problem. We emphasized the importance of yeast cells in the development of thermostable vaccines. In the end, we discussed why thermostable vaccines are required, not only in resource-poor countries but also for resource-rich countries . EXPERT OPINION: Temperature change can severely impact the stability of various life-saving vaccines. Therefore, there is a pressing need for the development of thermostable vaccines with a long shelf lives.

A global survey in the developmental landscape of possible vaccination strategies for COVID-19.

The development of COVID-19 vaccines was promptly regulated to ensure the best possible approach. By January 2022, 75 candidates reached preclinical evaluation in various animal models, 114 vaccines were in clinical trials on humans, and 48 were in the final testing stages. Vaccine platforms range from whole virus vaccines to nucleic acid vaccines, which are the most promising in prompt availability and safety. The USA and Europe have approved vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNa1273). So far, Pfizer-BioNTech, Moderna, Johnson & Johnson, AstraZeneca-University of Oxford, Sinopharm, Sinovac Biotech Gamaleya, Bharat Biotech, and Novavax have documented effective vaccines. Even with technological advances and a fast-paced development approach, many limitations and problems need to be overcome before a large-scale production of new vaccines can start. The Key is to ensure equal and fair distribution globally through regulatory measures. Recent studies link Bacillus Calmette-Guérin (BCG) vaccination programs and lower disease severity.

Immunotherapy for COVID-19: Evolving treatment of viral infection and associated adverse immunological reactions.

This review on COVID-19 immunotherapy enables a comparative analysis of the short-list of currently approved major vaccines. These include the Pfizer and Moderna first mRNA vaccines under FDA purview and the Oxford/AstraZeneca simian adenovirus-vectored vaccine (under UK-MHPRA guidance), all produced in record time, being safe and effective. The Pfizer and Moderna double dose vaccines have the clear edge in treatment efficacy, being in the 90% range compared to AstraZeneca in the average 70%. However, the AZ double dose vaccine has significant advantages with respect to lower cost and stability in storage. We enumerate several potential advances in the technology of the manufacturers: (1) combination vaccines such as testing AstraZeneca's product with a component of the Russian's Sputnik V to achieve durable immunity; (2) the potential for single dose vaccines coming on-line, and with Johnson & Johnson/Janssen; and (3) the need for refined thermotolerant formulations obviating the need for cold storage. As an adjunct to vaccinotherapy, affinity adsorption column technology is another facet recruited in the processing of corona convalescent plasma/cryosupernatant to concentrate neutralizing antibodies against the virus. Clinical trials, to date, of infected patients have been indeterminate as to whether plasmapheresis-based products are effective or not. This is due to the failure to standardize the composition of the plasma derived component, ambiguous clinical indications for use in human subjects, and inconsistent timing of administration in the course of the infection. Known T-cell lymphopenia, which is attendant to progressive viral infection and immune driven inflammation, may be a quantitative surrogate biological marker as to when to start treatment. This is not only for initiating plasmapheresis-based therapeutics but also the judicious selection of ancillary pharmaceuticals, ie. monoclonal antibodies, recombinant proteins and anti-viral drugs.

Vaccination against coronaviruses in domestic animals.

The current pandemic of COVID-19 has set off an urgent search for an effective vaccine. This search may well benefit from the experiences of the animal health profession in the development and use of coronavirus vaccines in domestic animal species. These animal vaccines will in no way protect humans against COVID-19 but knowledge of the difficulties encountered in vaccinating animals may help avoid or minimize similar problems arising in humans. Diverse coronaviruses can infect the domestic species from dogs and cats, to cattle and pigs to poultry. Many of these infections are controlled by routine vaccination. Thus, canine coronavirus vaccines are protective in puppies but the disease itself is mild and self-limiting. Feline coronavirus infections may be mild or may result in a lethal immune-mediated disease - feline infectious peritonitis. As a result, vaccination of domestic cats must seek to generate- protective immunity without causing immune-mediated disease. Vaccines against bovine coronavirus are widely employed in cattle where they protect against enteric and respiratory disease in young calves. Two major livestock species suffer from economically significant and severe coronavirus diseases. Thus, pigs may be infected with six different coronaviruses, one of which, porcine epidemic diarrhea, has proven difficult to control despite the development of several innovative vaccines. Porcine epidemic diarrhea virus undergoes frequent genetic changes. Likewise, infectious bronchitis coronavirus causes an economically devastating disease of chickens. It too undergoes frequent genetic shifts and as a result, can only be controlled by extensive and repeated vaccination. Other issues that have been encountered in developing these animal vaccines include a relatively short duration of protective immunity, and a lack of effectiveness of inactivated vaccines. On the other hand, they have been relatively cheap to make and lend themselves to mass vaccination procedures.

[Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future].

The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.