V1 Immunological Considerations for COVID-19 Vaccine Strategies

Ending COVID Part II Vaccines

The Evaluation of the Safety, Tolerability, and Effectiveness of Current Vaccines for SARS-COV-2/COVID-19

Vaccine design strategies regard a series of items including the selection of antigens, vaccine platforms, vaccination routes, regimen among others. The choice of a vaccine platform determines the relative immunogenic strength of vaccine-derived viral antigen, whether an immune adjuvant is required, and the relevant nature of protective immunity. These attributes also determine the suitability of a vaccine for a particular route of vaccination, and whether an additional prime–boost vaccination regimen is required to increase vaccine-mediated protective immunity and its durability.

As most individuals infected with severe acute respiratory syndrome CoV-2 (SARS-CoV-2) are asymptomatic or develop only mild symptoms. (COVID-19) vaccines are being developed towards an ultimate goal of global mass immunization.  The first area to observe is, vaccine safety, which is of paramount importance. Any indication of a lack of safety considerations could also fuel the antivaccination movement and vaccine hesitancy, which would jeopardize the desired effect of achieving herd immunity. 

Concerning herd immunity, specific statistics regarding the percentage amount (%) of how many in the population would need to be vaccinated, in order to create herd immunity should now be calculated. 

Range percentages from a high of 67% to a low of 10% vary as far as population percentage requirements to establish an environment of herd immunity. In addition percentages have to be determined for specific target groups who are impacted the most as far as the spread of the virus (elderly, immuno-compromised). Targeting these specific groups with preliminary vaccination recommendations should subside the overall impact, regarding demise data for SARS-Cov-2. 

In this regard, most of the current COVID-19 vaccine clinical trials were initially conducted in healthy adults aged 55 years or younger. Later stage trials including seniors are not being conducted at the same pace. The highly susceptible elderly populations and those with underlying medical conditions are in particular need of highly safe and effective vaccines. Once the appropriate vaccine as been determined for distribution within the United States, these populations are expected to receive it first. 

Innate immune memory (also known as trained immunity) is a recently recognized component of immunological memory that has implications for vaccine strategies83,84,168,169. Several live attenuated human vaccines induce trained immunity that can mediate non-specific protective responses to heterologous infections in addition to pathogen-specific adaptive immune memory168,169,170. The most well-studied human vaccine that induces trained immunity is the bacillus Calmette–Guérin (BCG) vaccine against tuberculosis171. BCG vaccination endows circulating monocytes with characteristics of trained immunity through epigenetic and metabolic rewiring of myeloid progenitors in the bone marrow169,172,173. These trained monocytes enhance protection against heterologous infections, including respiratory viral infection174,175,176. BCG may therefore offer a level of protection from  COVID-19, which might be supported by the observed inverse correlation between universal BCG vaccination and COVID-19 fatalities177. Several clinical trials are under way to assess the effects of BCG or measles vaccination on COVID-19 (ref.178).

A COVID-19 vaccine that can induce trained immunity might enhance early viral control by overcoming virus-imposed innate immune suppression and facilitating adaptive immune activation. The critical component is determining the presence of antibodies and long term stability.  

The early timing of action by trained immunity is of importance as the overproduction of cytokines by macrophages at later stages of COVID-19 can contribute to immunopathology. This is however not sufficient enough to circumvent the innate immune response that is created by the vaccine. 

Although it remains to be understood how to best harness trained immunity for COVID-19 vaccine strategies, recent evidence suggests that routes of microbial exposure or vaccination determine the tissue distribution of trained immunity83,84,169. 

As respiratory mucosal immunity is key to early clearance of severe acute respiratory syndrome (SARS-CoV-2), inducing trained immunity in alveolar macrophages and other innate cells83,179,180,181 through respiratory mucosal vaccination could be an effective strategy. Indeed, a human serotype 5 adenovirus-vectored vaccine delivered to the respiratory mucosa induces memory alveolar macrophages capable of trained immunity against heterologous infections85. However, it is unclear whether lung memory macrophages may be replaced by inflammatory monocytes in response to SARS-CoV-2.

These among other immunological considerations for developing an effective vaccine for SARS-CoV-2 are a starting point to consider.