BA.3 was originally discovered in northwestern South Africa.
This subvariant is a combination of mutations in BA.1 and BA.2 spike proteins.
Of the 33 mutations in the BA.3 lineage spike protein, 31 mutations are common to BA.1.
BA.3 is currently causing the lowest number of cases in these three lineages. It may have been due to the loss of six mutations (ins214EPE, S371L, G496S, T547K, N856K, and L981F) from BA.1 or obtaining two mutations from BA.2 (S371F and D405N).
After the initial two doses of the BNT162b2 (Pfizer) vaccine, the median pseudovirus neutralizing antibody titers against WA1/2020, BA.1, and BA.2 were 658, 29, and 24, respectively.
Six months after the initial vaccination, the median neutralizing antibody titers declined to 129 for WA1/2020 and to less than 20 for both BA.1 and BA.2.
Two weeks after the third dose (booster) of the BNT162b2 vaccine, the median neutralizing antibody titers increased substantially to 6539 for WA1/2020, 1066 for BA.1, and 776 for BA.2, indicating that the median neutralizing antibody titer against WA1/2020 was 6.1 and 8.4 times those for BA.1 and BA.2, respectively.
After the fourth dose, both Pfizer and Moderna vaccines induced IgG antibodies against SARS-CoV-2 receptor-binding domain and increased neutralizing antibody titers; each measure was increased by a factor of 9 to 10, to titers that were slightly higher than those achieved after the third dose, with no significant difference between the two vaccines.
Both vaccines induced an increase in live neutralization of the B.1.1.529 (omicron) variant and other viral strains by a factor of approximately 10, similar to the response after the third dose.
The fourth dose did not lead to substantial adverse events despite triggering mild systemic and local symptoms in the majority of recipients
Vaccine efficacy was estimated to be higher for the prevention of symptomatic disease (43% for BNT162b2 and 31% for mRNA-1273).
Most of the infected participants were potentially infectious, with relatively high viral loads.
A fourth dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease).
A comparison of the initial response to the fourth dose with the peak response to a third dose did not show substantial differences in humoral response or in levels of omicron-specific neutralizing antibodies.
Both LY-CoV016 (marketed as etesevimab) and LY-CoV555 (marketed as bamlanivimab), individually and in combination, lost neutralizing activity against omicron/BA.2 (NCD1288).
REGN10987 (marketed as imdevimab), which was previously shown to lose neutralizing activity against omicron/BA.1 (NC928) and omicron/BA.1.1 (NC929) had neutralizing activity against omicron/BA.2 (NCD1288).
The combination of REGN10987 and REGN10933 (marketed as casirivimab) also inhibited omicron/BA.2 but did not inhibit omicron/BA.1 or omicron/BA.1.1.
REGN10933, COV2-2196 (marketed as tixagevimab), and COV2-2130 (marketed as cilgavimab) neutralized omicron/BA.2.
S309 (the precursor of sotrovimab) had low neutralizing activity against omicron/BA.2.
All together, this study showed that some therapeutic monoclonal antibodies (REGN10987–REGN10933, COV2-2196–COV2-2130, and S309) have lower neutralizing activity against omicron/BA.2 than against earlier variant strains.
The susceptibilities of omicron/BA.2 (NCD1288) to remdesivir, molnupiravir, and nirmatrelvir were similar to those of the ancestral strain and other variants of concern.
Infection period of the Omicron variant
Recent analysis from the UK Health Security Agency suggests that the window between infection and infectiousness may be shorter for the Omicron variant than the Delta variant.
Data from recent outbreaks of Omicron demonstrate that the incubation period of Omicron may be as short as 3-5 days (compared to 5-7 days for the Delta variant and 7-14 days for the original SARS-CoV-2).