Booster vaccination counters the severity of Omicron breakthrough infections

Booster vaccination counters the severity

of Omicron breakthrough infections
By Neha Mathur Jul 21 2022
Reviewed by Aimee Molineux

In a recent study published in Science, researchers assessed a panel of seven

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines
currently available globally and in the United States (US) and immunity
acquired through the previous infection against all Omicron subvariants.

Study: Omicron spike function and neutralizing activity elicited by a

comprehensive panel of vaccines. Image Credit: BaLL LunLa/Shutterstock

Background
SARS-CoV-2's most recent variant of concern (VOC) Omicron, with its potential
to evade the host's infection-combating strategies, is fitter and more
transmissible than its predecessors. It has evolved into several sublineages, and
the most dangerous Omicron BA.5 sub-variant shall soon dominate globally by
replacing other variants. Due to the rise in breakthrough infections and the
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Booster vaccination counters the severity of Omicron breakthrough infections

enhanced transmissibility of Omicron BA.5., the US government is considering

recommending a second dose of booster vaccination for adults below 50 years
of age.

SARS-CoV-2 vaccines utilize the spike (S) glycoprotein (sometimes only the
receptor-binding domain (RBD)) or (inactivated) virus and an array of delivery
technologies. Although Omicron subvariants have severely blunted the
protective immunity induced by the primary vaccine series or prior infection,
preliminary studies have pointed to the potential of booster vaccination to elicit
neutralizing antibodies against Omicron subvariants.

About the study

In the present study, researchers first examined the functional impact of the
mutations in the Omicron subvariants S proteins – that gives it a crown-like
appearance and enables fusion with the host cells crucial for establishing an
infection. Next, they evaluated the neutralizing activity elicited by vaccines or
prior infection against all Omicron subvariants. They created vesicular stomatitis
virus (VSV) pseudotyped with the SARS-CoV-2 Wuhan-Hu-1 S harboring the
D614G, BA.2.12.1, BA.1, BA.2, or BA.4/5 mutations.

Further, the researchers used VeroE6 cells expressing transmembrane protease

serine 2 (TMPRSS2) to propagate VSVs in the presence of vaccinee or
convalescent plasma, obtained early in the pandemic. They determined a
plasma neutralizing geometric mean titer (GMT) of neutralizing activity against
any of the four tested Omicron sublineages. The researchers also evaluated the
Omicron subvariant neutralizing antibodies elicited by vaccines mRNA-1273,
BNT162b2, Ad26.COV2, AZD1222, NVX-CoV2373, Sputnik V, and BBIBP-CorV
vaccines. The primary vaccine series of six vaccines consisted of two doses,
except for Ad26.COV2.

They measured and compared the benefits of vaccine boosters on the plasma
neutralizing activity against the ancestral SARS-CoV-2 virus and the Omicron
subvariants. Additionally, they assessed and compared the benefits of
homologous or heterologous vaccine boosters.

Study findings
Biolayer interferometry (BLI) and surface plasmon resonance (SPR) results
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showed that the angiotensin-converting enzyme 2 (ACE2)-binding affinity of the

Omicron BA.4/5 RBD was the greatest among all the tested RBDs. It bound
ACE2 more than six times stronger than the ancestral SARS-CoV-2 Wuhan-Hu1
strain. Conversely, all Omicron subvariants were slower than Wuhan-Hu-1 and
the Delta VOC at fusing with the membrane on the host cell, a phenomenon
called fusogenicity. The researchers hypothesized that a more robust ACE2-
binding capacity compensated for Omicron's weaker fusogenicity.

Only five serum samples of the 24 early-pandemic samples had detectable

neutralizing activity against any of the Omicron sublineages tested, and even
their response was weak. Based on the magnitude of evasion of polyclonal
serum neutralizing antibody responses for Omicron sublineages in vaccinated
individuals, the authors confirmed that the Omicron BA.5 subvariant would be
the most immune evasive SARS-CoV-2 variant to date. Additionally, the type of
vaccine had little effect on the elicited neutralizing antibody responses against
Omicron sub-variants. Compared to BA.2 and BA.2.12.1, the authors observed
a consistently higher magnitude of neutralizing antibody responses for BA.1 and
BA.4 sub-variants.

After the primary vaccination, three subjects had detectable neutralizing activity
against Omicron sublineages in HEK293T/ACE2 target cells. However, all except
one participant had weak but detectable neutralizing activity against Omicron
VSV pseudotypes in VeroE6/TMPRSS2 cells. The finding confirmed the role of
target cell lines or viral entry routes in neutralization assays on the observed
GMT values.

Conclusions
Overall, all four Omicron sub-variants examined in the current study had
increased ACE2 binding affinity and decreased fusogenicity but exceptional
neutralizing antibody evading potential compared to the ancestral Wuhan-Hu-1
and Delta VOC. Together, the study data justify the rapid transmission of
Omicron sublineages worldwide and the reasons for the continuous rise in the
prevalence of the Omicron BA.4 and BA.5 sub-variants.

Furthermore, the current study highlighted that despite the exceptional immune
evading potential of Omicron subvariants, additional booster doses with
currently available vaccines could confer strong protection against severe
disease due to breakthrough infections. The study authors emphasized the

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importance of evaluating the time interval between vaccination doses to

increase the breadth and strength of the neutralizing antibody responses
against new and yet to emerge SARS-CoV-2 VOCs. They also stressed the
importance of continuous surveillance to detect new SARS-CoV-2 variants early.
Most importantly, the authors recommended frequent evaluations of current
COVID-19 vaccines and sustained efforts to develop and test new vaccines as a
preparedness measure against the entire contingency of sarbecoviruses.

Journal reference:
John E. Bowen, et al. (2022). Omicron spike function and neutralizing
activity elicited by a comprehensive panel of vaccines. Science. doi:
10.1126/science.abq0203 https://www.science.org/doi/10.1126/scie
nce.abq0203

Written by

Neha Mathur
Neha is a digital marketing professional based in Gurugram, India. She has a Master’s
degree from the University of Rajasthan with a specialization in Biotechnology in
2008. She has experience in pre-clinical research as part of her research project in
The Department of Toxicology at the prestigious Central Drug Research Institute
(CDRI), Lucknow, India. She also holds a certification in C++ programming.

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