Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination

Abstract

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

“…The ability of Delta-elicited sera to cross-neutralize Omicron BA.1 is debated [ 48 , 49 , 68 , 80 , 91 , 92 , 93 , 94 , 117 ]. Our results clearly indicate that Gamma- or Delta-breakthrough sera with a high neutralizing activity against these VOCs are able to cross-neutralize Omicron BA.1, in agreement with previous studies [ 49 , 93 , 94 , 118 ], although our data only apply to vaccinated BTI infected with Delta and we cannot infer whether they extend to BTIs infected with other VOCs. Since breakthrough infection acts as a booster, this observation is congruent with the restoration of neutralizing ability induced by booster vaccination [ 27 , 28 , 44 , 46 , 48 , 57 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ].…”

Omicron Booster in Ancestral Strain Vaccinated Mice Augments Protective Immunities Against Both Delta and Omicron Variants

“…Meanwhile, we found that the mice boosted with the Omicron S DNA vaccine also maintained relatively higher RBD binding antibody and neutralizing antibody responses against the Delta variant. Our finding is consistence with most recent studies showing that Omicron infection alone did not induce superior cross-reactive antibody responses, while Omicron infection in previously vaccinated individuals can significantly enhance cross-protective neutralizing antibody responses ( 23 , 37 ). These observations suggest that a booster of an Omicron-matched vaccine might help to boost broadly neutralizing antibody responses.…”

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

“…[3][4][5][6][7] Omicron and omicron subvariants continue to cause significant morbidity and mortality and re-infection with omicron or a subvariant is possible, especially in unvaccinated individuals. [8][9][10] Immunization with an mRNA-1273 50-µg booster dose increases neutralizing antibody responses against variants and booster doses enhance vaccine effectiveness against Covid-19. [11][12][13][14][15][16] Nonetheless, effectiveness of the currently authorized vaccines against omicron is decreased compared to other variants [17][18][19][20] and consequently, a second booster dose was authorized in the US for immunocompromised individuals and adults >50 years of age in the midst of omicron waves.…”