ABSTRACT
Despite the current advances in global vaccination against SARS-CoV-2, boosting is still required to sustain immunity in the population, and the induction of sterilizing immunity remains as a pending goal. Low-cost oral immunogens could be used as the basis for the design of affordable and easy-to-administer booster vaccines. Algae stand as promising platforms to produce immunogens at low cost, and it is possible to use them as oral delivery carriers since they are edible (not requiring complex purification and formulation processes). Herein, a Chlamydomonas-made SARS-CoV-2 RBD was evaluated as an oral immunogen in mice to explore the feasibility of developing an oral algae-based vaccine. The test immunogen was stable in freeze-dried algae biomass and able to induce, by the oral route, systemic and mucosal humoral responses against the spike protein at a similar magnitude to those induced by injected antigen plus alum adjuvant. IgG subclass analysis revealed a Th2-bias response which lasted over 4 months after the last immunization. The induced antibodies showed a similar reactivity against either Delta or Omicron variants. This study represents a step forward in the development of oral vaccines that could accelerate massive immunization.
ABSTRACT
BACKGROUND: As of early 2022, the Omicron variants are the predominant circulating lineages globally. Understanding neutralizing antibody responses against Omicron BA.1 and BA.2 after vaccine breakthrough infections will provide insights into BA.2 infectivity and susceptibility to subsequent reinfection. METHODS: Live virus neutralization assays were used to study immunity against Delta and Omicron BA.1 and BA.2 variants in samples from 86 individuals, 24 unvaccinated (27.9%) and 62 vaccinated (72.1%), who were infected with Delta (n = 42, 48.8%) or BA.1 (n = 44, 51.2%). Among the 62 vaccinated individuals, 39 were unboosted (62.9%), whereas 23 were boosted (37.1%). RESULTS: In unvaccinated infections, neutralizing antibodies (nAbs) against the three variants were weak or undetectable, except against Delta for Delta-infected individuals. Both Delta and BA.1 breakthrough infections resulted in strong nAb responses against ancestral wild-type and Delta lineages, but moderate nAb responses against BA.1 and BA.2, with similar titers between unboosted and boosted individuals. Antibody titers against BA.2 were generally higher than those against BA.1 in breakthrough infections. CONCLUSIONS: These results underscore the decreased immunogenicity of BA.1 compared to BA.2, insufficient neutralizing immunity against BA.2 in unvaccinated individuals, and moderate to strong neutralizing immunity induced against BA.2 in Delta and BA.1 breakthrough infections.