Rationale• Rapid manufacturing and effective distribution of sufficient quantities of vaccines is paramount to launch a successful vaccination campaign that will successfully achieve herd immunity to interrupt the pandemic crisis.• The fundamental objective driving COVID-19 vaccine deployment is to ensure that all people have fair access to safe and effective COVID-19 vaccines.• The purpose of Part 4 of this series is to highlight the logistical and ethical challenges of the supply and distribution chain of COVID-19 vaccines.Key points• All phases of the COVID-19 vaccination campaign merits strong consideration from an ethical and logistical perspective.• Vaccines must be authorised by regulatory authorities before use.• Governmental implementation bottlenecks are the cause of the inability to vaccinate at-risk populations rapidly.• Productivity and manufacturing of mRNA-based vaccines remain low, and ultra-cold chain requirements impose significant storage and distribution challenges.• Viral vector-based vaccines are based on proven technology and expected to yield significantly higher annual volumes.• Recombinant protein subunit vaccines can be easily scaled up, are reasonably stable and easier to manage, but development is currently running months behind schedule.• Live attenuated and whole inactivated virus vaccines require regulatory-approved biosafety level 3 (BSL-3) facilities for development and manufacturing, thus have more safety hurdles, are more complicated and slower to develop, and therefore unpredictable to manufacture.• An effective vaccination campaign requires adequate procurement of vaccines and political will.• Health care workers and elderly adults are the highest priorities for vaccination.• Exposing vaccine distribution and implementation plans to scrutiny is critical.• Allocation of limited vaccines should be prioritised and based on the ethical principles of maximising benefits, minimising harms, fair and equal access, transparency, informed consent and trust. • Public trust can only be ensured through transparent communications and consistently applied allocation of safe, effective, and fair vaccines to everyone.• Safety and public trust are critical considerations in vaccine acceptance.• Health care professionals are the most trusted source of information.Public health implications• Access to vaccines for global distribution before the end of 2021 will be a task of unprecedented proportions.• Experts recommend that governments invest in a more expansive and diversified portfolio of vaccines.• Many countries are under-resourced with vulnerable high-risk communities.• Multiple stakeholders are driving a global approach to equitable access.• Public distrust, anti-vaccine messaging, and vaccine hesitancy are a significant concern to vaccine campaign efficacy to contain the pandemic.

Rationale• Developing and deploying safe and effective COVID-19 vaccines are faced with many challenges and unanswered questions.• Massive amounts of heterogenic scientific data are being generated that are needed rapidly to advance vaccine development, protect people and restore normality. • The purpose of Part 3 of this four-part series is to review the scientific considerations related to key challenges associated with COVID-19 vaccines and immune protection with the focus of making this data more meaningful and open for clinicians.Key points• The primary immunogen (antigen) required to induce neutralising antibodies (humoral) and T cell (cellular) immune responses is the S-protein fragment of SARS-CoV-2. • Currently, the evidence is firmly pointing towards neutralising antibodies, being more critical for protection.• Long-term protective or durable immune memory is driven by virus-specific T cell and B cell responses (adaptive immunity).• Circulating antibody titres are not predictive of T cell immune memory.• Durable immune memory is a crucial factor to sustain herd immunity.• Adjuvants are added to certain vaccines to provoke a more robust and durable immune response.• Adjuvants that provoke TH1-biased immune responses are preferred. • 90% of adults are seropositive for 'common cold' CoV strains.• There is a cross-reactivity between specific T cell of SARS-CoV-2 and 'common cold' CoV's.• Prior infection with 'common cold' can play a potentially protective role.• Seropositive individuals present with a rapid and higher antibody immune response after a single dose with an mRNA vaccine.• Vaccine-induced immune responses resulting in non-neutralising antibodies, low antibody titres, and abnormal T cell responses (TH2- biased) are potential risks for serious enhanced disease events but unlikely events.• Vaccine strategies aimed at inducing high titres on neutralising antibodies and TH1- biased immune responses reduce the risk of serious adverse events.• Emerging variants of concern are extremely infectious, highly transmissible and threatens the protective efficacy of current vaccines.Public health implications• A rapid global vaccination campaign combined with standard mitigation measures to stop transmission is the best defence against the emergence of further SARS-CoV-2 variants and the safest way to attain herd immunity.• Booster immunisations may be required to promote or improve the durability and strength of vaccine immunity.