University of Hong Kong: Timely booster vaccination reduces omicron breakout infections and COVID-19 severity

Researchers from the AIDS Institute of the Department of Microbiology, The University of Hong Kong's School of Clinical Medicine and the State Key Laboratory of Emerging Infectious Diseases found that timely vaccination with coronavirus vaccine, or BNT162b2 vaccine, is critical for inducing activation of virus-specific memory B cells and omicron cross-reactive T cell responses, significantly reducing the frequency and severity
of breakthrough infections.

In people who received three doses of the vaccine, the neutralizing antibody efficacy of BA.
2.
12.
1 and BA.
4/5 was enhanced
by BA.
2 breakthrough infection and bivalent booster vaccination.
The research paper has now been published in The Lancet Regional Health—Western Pacific
.

Since the end of 2021, the omicron variant of the new coronavirus has erupted in the fifth and largest wave of the epidemic in Hong Kong, the "city of masks for all" in the world, with more than 2 million infections and more than 10,000 deaths
.
Omicron BA.
2 dominated the fifth wave due to its high transmissibility and immune avoidance, resulting in a mortality rate of 14.
39%
among unvaccinated elderly people aged 80 years and older.

However, most pre-vaccinated people develop mild clinical symptoms
after BA.
2 breakthrough infection.
Because CoronaVac (CorV) is less immunogenic than BNT162b2 (BNT), it is critical
to determine how vaccine-induced immune responses protect omicron BA.
2 from breakthrough infection.
In addition, with the subsequent entry of BA.
4/5 and other variants into Hong Kong, the immune response promoted by BA.
2 breakthrough infection should be tested for cross-reactive neutralizing antibodies
against BA.
4/5 and other variants.

Therefore, the researchers investigated the vaccine efficacy
of omicron BA.
2 breakthrough infection in 470 local civil servants who had received at least two doses of BNT or CorV vaccine before BA.
2 arrived in Hong Kong.
Antibody and cellular immune responses after three doses of vaccination are associated
with clinical features of BA.
2 infection.
The team found that timely third-dose vaccination provided better protection and a lower
incidence of breakthrough BA.
2 infection.

Investigations of immune responses to the three-dose vaccination cohort revealed that spike(S)-specific memory B cells and omicron cross-reactive T cell responses activated by the third dose were associated with a reduction in breakthrough infection and disease severity rather than with vaccine type
.
In addition, the frequency of s-specific activation of memory B cells in infected vaccines was significantly lower than in uninfected vaccines prior to vaccine breakthrough infection, and the number of s-specific CD4 T cells was inversely correlated
with viral clearance time.
Critically, in all vaccines tested, BA.
2 breakthrough infection enhanced cross-reactive memory B cells, enhancing cross-neutralizing antibodies
to omicron sublines, including BA.
2.
12.
1 and BA.
4/5.

"Our findings highlight the importance of
activating memory B cells and omicron cross-reactive T cell responses in preventing omicron BA.
2 disease.
" Dr Zhou Runhong, Research Assistant Professor, Department of Microbiology, School of Clinical Medicine, HKU, said, "Since BA.
2 breakthrough infections are mainly retrospective vaccine-induced antibodies against ancestral strains, the importance of
monitoring cross-protection against breakthrough infections and emerging virus variants induced by novel bivalent COVID-19 vaccines is emphasized.
"

Professor Chen Zhiwei, Director of the AIDS Institute, Department of Microbiology, School of Clinical Medicine, Hong Kong Medical University, who led the study, said: "It is encouraging that coronavirus-induced memory B cells and T cells are rapidly recalled to ward off omicron breakthrough infection
.
However, we should strengthen public surveillance for escape variants of highly pathogenic viruses to prevent them from attacking vaccinated people
.
”

Editor's note:

Last July, a survey provided by the Epidemiology Unit of the National Institute of Lisbon, Portugal, found no difference in the chances of vaccination between BA.
5 and BA.
2 cases in the Portuguese adult population, indicating that the effectiveness of the vaccine against BA.
5 infection was similar
to that of BA.
2.
The BA.
5 lineage is associated with
a higher chance of reinfection compared with BA.
2.
This finding suggests that prior infection has a reduced
protective effect against BA.
5 compared to BA.
2.

Comparing the risk of hospitalization and death between vaccinated and unvaccinated, for hospitalization outcomes, it was found that BA.
5 cases vaccinated with a booster dose were 3.
4-fold more likely to be hospitalized than BA.
2 cases, and the results showed that immune evasion on the BA.
5 lineage was higher
than BA.
2.
Despite being less effective compared to BA.
2, COVID-19 booster vaccination still provides substantial protection
against the serious consequences of BA.
5 infection.

Recently, Moderna also released clinical results containing omicron BA.
4/BA5 bivalent enhancer mRNA-1273.
222 safety and immunogenicity (ClinicalTrials.
gov Identifier: NCT04927065), an ongoing phase II/III trial in which 50 μg mRNA-1273.
222 (Wuhan-Hu-1 and omicron) were sent BA.
4/BA.
5 spike mRNAs 25 μg each) were compared with 50 μg mRNA-1273, which as a second enhancer was used in
adults who had previously received 2 injections (100 μg) of the primary series and the first booster (50 μg) mRNA-127.
The primary goal is to enhance safety and immunogenicity
at the next 28 days.

Participants received 50 μg mRNA-1273 (n=376) or mRNA-1273.
222 (n=511) as a second booster dose
。 In participants without prior SARS-CoV-2 infection, the geometric mean titers (GMT[95% confidence interval]) of the neutralizing antibodies of Omicron BA.
4/BA.
5 and SARS-CoV-2 D614G were significantly higher than mRNA-1273.
222 (2324.
6 [19212.
2-2812.
7] and 7322.
4 [6386.
2-8395.
7]) at day 29 (488.
5 [ 427.
45-558.
4] and 5651.
4 (5055.
7-6317.
3).

A randomly selected subset of participants (N=60) in the mRNA-1273.
222 group also exhibited cross-neutralization
of the emerging omics variants BQ.
1.
1 and XBB.
1.
No new security issues
were identified with mRNA-1273.
222.

Vaccine effectiveness was not assessed in this study; In an exploratory analysis, 1.
6% (8/511) of mRNA-1273.
222 receptors were infected with COVID-19 after the booster
.

ConclusionCompared with mRNA-1273, the vaccine containing divalent omicron BA.
4/BA5-mRNA-1273.
222 has a better response to BA.
4/BA.
5 neutralizing antibodies and has no safety problems
.