Leading experts suggest comprehensive post-efficacy strategy required after demonstrated efficacy of COVID-19 vaccines in Nature Medicine commentary

Questions regarding vaccine longer-term efficacy, optimization, protection, safety and surveillance remain unanswered
“It is still unknown whether the vaccines prevent infection or transmission, apart from proven prevention of disease,” IVI Director General Dr. Jerome Kim
Timely and coordinated execution of post-efficacy tasks will bring the pandemic to an effective and efficient close
Read the full article in Nature Medicine here, written by Jerome H. Kim, Florian Marks, and John D. Clemens

With much-awaited COVID-19 vaccination now underway in a number of countries, a team of leading vaccine experts addresses lingering questions and issues and suggests the need for a comprehensive post-efficacy strategy for the next steps to ensure vaccination of the global population and end the pandemic.

“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,” said Dr. Jerome Kim, Director General of the International Vaccine Institute (IVI) in a recent Nature Medicine commentary co-authored by Dr. John Clemens (former Director General of IVI and Executive Director of icddr,b), and Dr. Florian Marks, Deputy Director General of IVI.

“For instance, with the current estimates on the required level of effective population immunity (60-70%), the world needs 10-11 billion doses to interrupt transmission for 8 billion people with a two-dose regimen. With an estimated global production of 2 to 4 billion doses per year, some groups estimate that it will be 2023-2024 before enough vaccine can be manufactured.

The authors warn “An access gap for COVID-19 vaccines would have dramatic consequences.” An analysis by the Duke Global Health Innovation Center suggests that more than 8 billion doses of vaccines [while] under development from Western manufacturers were pre-ordered by high-income countries. However, one modeling study provides data that if high-income countries exclusively acquire the first 2 billion doses and disregard vaccine equity, the number of COVID-19 deaths could double.

Will misinformation, vaccine hesitancy, politics, deception and division undermine efforts to vaccinate communities and lower the burden of COVID-19? “Initially, it is important for vaccination to be seen as one part of a comprehensive package of COVID-19 prevention, which will include masks, distancing, hygiene and preparedness of healthcare facilities for an unknown period,” the authors said. “More importantly, for vaccination campaigns to be successful, governments must anticipate these issues and build trust and consensus around the safety, efficacy and necessity of vaccination.”

“Vaccines are an important tool, but they must be wielded effectively and used in conjunction with other evidence-based public health measures to be decisive,” said Dr. Kim. “With effective vaccination and prevention efforts, we hope to see the ‘end of the beginning’.”

Furthermore, the authors stress that additional scientific questions about the vaccines should be answered to potentially make future COVID-19 campaigns more practical by allowing national programs time to plan and execute more effectively. They include the optimization of vaccination regimens, booster doses, the correlates of protection, vaccine effectiveness, safety and enhanced surveillance.

“Regardless of the licensure achievement via current phase 3 trials, there are substantial uncertainties about the practicality of COVID-19 vaccines and studies done after licensure, including the level of protection of both vaccinated and non-vaccinated individuals in entire targeted populations are needed,” Dr. John Clemens said. “The timely and coordinated execution of these post-efficacy tasks will assist bringing the pandemic to an effective, and efficient, close.”

For example,

We do not know yet whether protective immune responses are durable; perhaps identification of ‘correlates of immune protection’ will determine what level of an immune biomarker is necessary for protection.

We also do not know whether a SARS-CoV-2 vaccine, based on strains isolated in 2019 and 2020, will continue to protect against SARS-CoV-2 strains circulating in 2021 or 2022.

Additional booster doses might be necessary to extend the duration of protection; we do not know whether primary series and booster doses can or should be different. It is also unclear whether previously infected persons would benefit from vaccination, although, at this point, vaccination against SARS-CoV-2 should occur irrespective of infection status.

There are certain safety-related events that due to rarity or pathogenesis, might be detected only during longer-term surveil lance or adverse events after immunization.

Because pregnant women and children have not been included in clinical trials of COVID-19 vaccines, these studies must eventually be completed, both for efficacy and importantly, for safety.

“We do not have sufficient evidence to say that either new introductions or genetic drift might produce a variant virus requiring a different vaccine strain,” they said.

“It is still unknown whether the vaccines prevent infection or transmission, despite their proven efficacy for the prevention of the disease (or symptoms),” Dr. Kim said.

“The current phase 3 trials are powered to detect protection against symptomatic infections.”

However, protection against severe COVID-19 disease and mortality is a key goal of implementing a COVID-19 vaccine in practice, and knowledge of vaccine protection against overall COVID-19 disease might not permit prediction of protection against severe disease,” the authors noted, suggesting the need for post-efficacy effectiveness study and related measures.

Read the full article in Nature Medicine here.

Kim, J.H., Marks, F. & Clemens, J.D. Looking beyond COVID-19 vaccine phase 3 trials. Nat Med (2021). https://doi.org/10.1038/s41591-021-01230-y