TABLE 1.

Categories of vaccines for protection against SARS-CoV-2 infection and/or disease^a

Vaccine category	Safetyb	Speed and ease of production	Logistics of global distribution	Potential for NAb induction	Potential for cell-mediated immunityc
Live attenuated virus	Substantial concerns	NAd	NA	Probably high	Probably good
Inactivated virus	Some concernse	Intermediate	Feasible	Moderate	Poor
Nonreplicating virus vector (recombinant DNA virus)	High	High	Feasible	Weak	Probably good
DNA plasmid given by electroporation	High	High	Some concernsf	Very weak	Probably good
mRNA	High	High	May be difficultg	Weak	Probably good
Soluble or nanoparticle S- or RBD-protein, with adjuvant	High	Lowh	Feasible	High	Poor

^aFor a complete list of vaccine candidates in preclinical and phase 1/2/2b/3 clinical trials, see https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. All the categories listed in the table are represented except live attenuated virus, which is a traditional and widely used method that is not being tested for SARS-CoV-2. How the various categories are summarized in this table is based on the small amount of available data, combined with general experience of how similarly designed vaccines have performed against other viral pathogens. Nonetheless, there are considerable uncertainties behind some of the assessments in the table. Emerging clinical trial data will determine whether they are accurate.

^bSafety indicates the likelihood the vaccine will be tolerated without serious adverse effects in the absence of infection. For all categories, there are substantial uncertainties about the risk of exacerbated pathogenesis postinfection, by ADE and VAERD mechanisms (see the text). These risks may be the greatest for vaccines that induce only low NAb titers and/or a high non-NAb/NAb ratio.

^cMost emphasis has been placed on the induction of NAbs, although some data on cellular immune responses are emerging from animal studies and more will be obtained in human trials. Attempts to induce cytotoxic T cells might include immunization with viral proteins other than S, including nonsurface exposed internal ones (e.g., the N-protein). Extrapolation from other vaccines leads to the assessments listed.

^dNA, not applicable. There are no known plans to produce this type of vaccine.

^eFor a killed virus vaccine to be safe, the pathogen must be fully inactivated. Historically, inactivation has sometimes been incomplete (e.g., with polio vaccines).

^fDelivering DNA vaccines into muscles via electroporation is a relatively complex procedure compared to direct injection via needles or oral delivery.

^gThe ease with which mRNA vaccines can be formulated and distributed has not been widely discussed. However, if these vaccines turn out to be unstable at ambient temperatures, it will be challenging to distribute frozen or chilled stocks.

^hGeneral experience suggests that producing a stable cell line and using it to make large stocks of recombinant proteins under good manufacturing process conditions can take 1 to 2 years.