As of February 2022, SARS-CoV-2 is still one of the most
serious public health threats due to its high mortality rate and
rapid spread of novel variants. Since the first outbreak in 2019,
general understanding of SARS-CoV-2 has been improved
through basic and clinical studies; however, knowledge gaps
still exist in our understanding of the emerging novel SARSCoV-
2 variants, which impacts the corresponding development
of vaccines and therapeutics. Especially, accumulation of
mutations in SARS-CoV-2 and rapid spread in populations
with previous immunity has resulted in selection of variants
that evade the host immune response. This phenomenon threatens
to render current SARS-CoV-2 vaccines ineffective for
controlling the pandemic. Proper animal models are essential
for detailed investigations into the viral etiology, transmission
and pathogenesis mechanisms, as well as evaluation of the
efficacy of vaccine candidates against recent SARS-CoV-2
variants. Further, the choice of animal model for each research
topic is important for researchers to gain better knowledge
of recent SARS-CoV-2 variants. Here, we review the advantages
and limitations of each animal model, including mice,
hamsters, ferrets, and non-human primates, to elucidate variant
SARS-CoV-2 etiology and transmission and to evaluate
therapeutic and vaccine efficacy.