Zapomeran

Zapomeran is composed of a self-amplifying mRNA encoding the spike protein of SARS-CoV-2, encapsulated in lipid nanoparticles. The self-amplifying mRNA is designed to produce extra copies of mRNA within the host cells after intramuscular injection, to achieve enhanced expression of the spike protein antigen. This gives rise to neutralising antibody and cellular immune responses to the spike antigen, which contributes to protection against COVID-19. The mRNA self-amplification process is transient and does not generate infectious particles.

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat-dose toxicity and reproductive and developmental toxicity.

General toxicity

A general toxicity study was conducted with zapomeran in rabbits (intramuscularly receiving a total of 3 doses, each exceeding the human dose, once every 2 weeks).

Transient increases in mean body temperature (increases of up to ~1.7°C), changes in laboratory tests (erythroid changes consistent with decreased erythropoiesis secondary to inflammation, minimally or mildly decreased platelet counts, minimally increased neutrophil and/or monocyte counts, mildly or moderately increased fibrinogen, and minimally increased globulin and/or minimally decreased serum albumin and increases in serum cytokines), as well as inflammatory findings in the spleen, lymph nodes (increased lymphocyte cellularity), consistent with an inflammatory response were observed.

Genotoxicity/carcinogenicity

Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine (lipids and mRNA) are not expected to have genotoxic potential.

Reproductive toxicity

Reproductive and developmental toxicity was investigated in rabbits in a combined fertility, embryo- foetal, and postnatal development study where female rabbits were intramuscularly vaccinated prior to mating, and during gestation (receiving 5 doses of vaccine each exceeding the human dose spanning between premating day 28 and gestational day 28). SARS-CoV-2 neutralising antibody responses were present in maternal animals from prior to mating to the end of the study on gestational day 28 as well as in foetus and offspring, indicating placental transfer of the maternal antibodies.

There were no vaccine-related effects noted on female fertility, development of the embryo and foetus or postnatal growth and development. No zapomeran data for excretion into milk are available.