Factors, enablers and challenges for COVID-19 vaccine development.

The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators and industry to overcome traditional challenges for the development of vaccine candidates and to reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical development and regulatory reviews were among the key factors that contributed to accelerating the development and approval of COVID-19 vaccines. The rapid development of COVID-19 vaccines benefited of previous scientific innovations such as mRNA and recombinant vectors and proteins. This has created a new era of vaccinology, with powerful platform technologies and a new model for vaccine development. These lessons learnt highlight the need of strong leadership, to bring together governments, global health organisations, manufacturers, scientists, private sector, civil society and philanthropy, to generate innovative, fair and equitable access mechanisms to COVID-19 vaccines for populations worldwide and to build a more efficient and effective vaccine ecosystem to prepare for other pandemics that may emerge. With a longer-term view, new vaccines must be developed with incentives to build expertise for manufacturing that can be leveraged for low/middle-income countries and other markets to ensure equity in innovation, access and delivery. The creation of vaccine manufacturing hubs with appropriate and sustained training, in particular in Africa, is certainly the way of the future to a new public health era to safeguard the health and economic security of the continent and guarantee vaccine security and access, with however the need for such capacity to be sustained in the interpandemic period.

Vaccine access, equity and justice: COVID-19 vaccines and vaccination.

Although significant progress has been made in achieving goals for COVID-19 vaccine access, the quest for equity and justice remains an unfinished agenda. Vaccine nationalism has prompted calls for new approaches to achieve equitable access and justice not only for vaccines but also for vaccination. This includes ensuring country and community participation in global discussions and that local needs to strengthen health systems, address issues related to social determinants of health, build trust and leverage acceptance to vaccines, are addressed. Regional vaccine technology and manufacturing hubs are promising approaches to address access challenges and must be integrated with efforts to ensure demand. The current situation underlines the need for access, demand and system strengthening to be addressed along with local priorities for justice to be achieved. Innovations to improve accountability and leverage existing platforms are also needed. Sustained political will and investment is required to ensure ongoing production of non-pandemic vaccines and sustained demand, particularly when perceived threat of disease appears to be waning. Several recommendations are made to govern towards justice including codesigning the path forward with low-income and middle-income countries; establishing stronger accountability measures; establishing dedicated groups to engage with countries and manufacturing hubs to ensure that the affordable supply and predictable demand are in balance; addressing country needs for health system strengthening through leveraging existing health and development platforms and delivering on product presentations informed by country needs. Even if difficult, we must converge on a definition of justice well in advance of the next pandemic.

COVID-19 vaccines and the pandemic: lessons learnt for other neglected diseases and future threats.

Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while low and middle-income countries (LMICs) were pushed to the back of the queue and relied more heavily on adenoviral vector, inactivated virus and recombinant protein vaccines. To prevent this from occurring in future pandemics, it is essential to expand the scale-up capacity for both traditional and new vaccine technologies at individual or simultaneous hubs in LMICs. In parallel, a process of tech transfer of new technologies to LMIC producers needs to be facilitated and funded, while building LMIC national regulatory capacity, with the aim of several reaching 'stringent regulator' status. Access to doses is an essential start but is not sufficient, as healthcare infrastructure for vaccination and combating dangerous antivaccine programmes both require support. Finally, there is urgency to establish an international framework through a United Nations Pandemic Treaty to promote, support and harmonise a more robust, coordinated and effective global response.

Vaccines and therapeutics for immunocompromised patients with COVID-19.

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.

Leveraging lessons learned from the COVID-19 pandemic for HIV.

The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.

Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database.

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

Supply and delivery of vaccines for global health.

Vaccines developed in high-income countries have been enormously successful in reducing the global burden of infectious diseases, saving perhaps 2.5 million lives per year, but even for successful cases, like the rotavirus vaccine, global implementation may take a decade or more. For unincentivized vaccines, the delays are even more profound, as both the supply of a vaccine from developing country manufacturers and vaccine demand from countries with the high disease burdens have to be generated in order for impact to be manifest. A number of poverty-associated infectious diseases, whose burden is greatest in low-income and middle-income countries, would benefit from appropriate levels of support for vaccine development such as Group A Streptococcus, invasive non-typhoid salmonella, schistosomiasis, shigella, to name a few. With COVID-19 vaccines we will hopefully be able to provide novel vaccine technology to all countries through a unique collaborative effort, the COVAX facility, led by the World Health Organization (WHO), Gavi, and the Coalition for Epidemic Preparedness Innovations (CEPI). Whether this effort can deliver vaccine to all its participating countries remains to be seen, but this ambitious effort to develop, manufacture, distribute, and vaccinate 60-80% of the world's population will hopefully be a lasting legacy of COVID-19.

Current approaches to HIV vaccine development: a narrative review.

INTRODUCTION: The development of an effective vaccine to protect against HIV is a longstanding global health need complicated by challenges inherent to HIV biology and to the execution of vaccine efficacy testing in the context of evolving biomedical prevention interventions. This review describes lessons learnt from previous efficacy trials, highlights unanswered questions, and surveys new approaches in vaccine development addressing these gaps. METHODS: We conducted a targeted peer-reviewed literature search of articles and conference abstracts from 1989 through 2021 for HIV vaccine studies and clinical trials. The US National Library of Medicine's Clinical Trials database was accessed to further identify clinical trials involving HIV vaccines. The content of the review was also informed by the authors' own experience and engagement with collaborators in HIV vaccine research. DISCUSSION: The HIV vaccine field has successfully developed multiple vaccine platforms through advanced clinical studies; however, the modest efficacy signal of the RV144 Thai trial remains the only demonstration of HIV vaccine protection in humans. Current vaccine strategies include prime-boost strategies to improve elicitation of immune correlates derived from RV144, combination mosaic antigens, novel viral vectors, antigens designed to elicit broadly neutralizing antibody, new nucleic acid platforms and potent adjuvants to enhance immunogenicity across multiple classes of emerging vaccine candidates. CONCLUSIONS: HIV vaccine developers have applied lessons learnt from previous successes and failures to innovative vaccine design approaches. These strategies have yielded novel mosaic antigen constructs now in efficacy testing, produced a diverse pipeline of early-stage immunogens and novel adjuvants, and advanced the field towards a globally effective HIV vaccine.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

A new Korean Research Investment for Global Health Technology (RIGHT) Fund to advance innovative neglected-disease technologies.

In 2018, the government of the Republic of Korea (ROK), South Korean life science companies, and a group of international funders led by the Bill & Melinda Gates Foundation launched a new and innovative funding agency to support neglected-disease research and development (R&D). The new venture is known as the Research Investment for Global Health Technology (RIGHT) Fund.

Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

Vaccine development for emerging infectious diseases.

Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons. The unprecedented scale and rapidity of dissemination of recent emerging infectious diseases pose new challenges for vaccine developers, regulators, health authorities and political constituencies. Vaccine manufacturing and distribution are complex and challenging. While speed is essential, clinical development to emergency use authorization and licensure, pharmacovigilance of vaccine safety and surveillance of virus variants are also critical. Access to vaccines and vaccination needs to be prioritized in low- and middle-income countries. The combination of these factors will weigh heavily on the ultimate success of efforts to bring the current and any future emerging infectious disease pandemics to a close.

Looking beyond COVID-19 vaccine phase 3 trials.

After the recent announcement of COVID-19 vaccine efficacy in clinical trials by several manufacturers for protection against severe disease, a comprehensive post-efficacy strategy for the next steps to ensure vaccination of the global population is now required. These considerations should include how to manufacture billions of doses of high-quality vaccines, support for vaccine purchase, coordination of supply, the equitable distribution of vaccines and the logistics of global vaccine delivery, all of which are a prelude to a massive vaccination campaign targeting people of all ages. Furthermore, additional scientific questions about the vaccines remain that should be answered to improve vaccine efficacy, including questions regarding the optimization of vaccination regimens, booster doses, the correlates of protection, vaccine effectiveness, safety and enhanced surveillance. The timely and coordinated execution of these post-efficacy tasks will bring the pandemic to an effective, and efficient, close.

SARS-CoV-2 vaccine development, access, and equity.

Over the past 9 mo, with 34 million infections and 1 million deaths, the COVID-19 pandemic has levied a grisly toll. Some countries, through political will and social organization, have successfully reduced the number of infections and deaths, but the global scale of loss reflects the difficulty of translating these approaches in other countries. An effective SARS-CoV-2 vaccine presents a technological solution to the failure of social and political ones. Vaccines are, however, not a silver bullet, but a safe, cost-effective, and globally applicable tool that will require a substantial effort-cooperation, commitment, time, and funding-to be effective.