Science's annual breakthrough respiratory syncytial virus RSV vaccine: 2023 finally ushered in the harvest season!

January 11, 2023 /eMedClub News/-- At the end of last year, Science announced the top ten scientific breakthroughs of 2022, among which RSV vaccines made breakthrough progress Successfully selected
.
Respiratory syncytial virus (RSV) is a common respiratory virus that is one of the main causes of lower respiratory tract infections, bronchitis and pneumonia in infants, the elderly and immunocompromised patients, and its prevalence is comparable to that of influenza viruses
.
According to statistics, about 34 million children under the age of five are infected worldwide every year, and about 3% to 7% of the elderly will be infected with RSV
.

In the post-pandemic world, the RSV virus has shown a multi-point outbreak trend, with cases rising in the US and Canada, and the number of RSV patients in the UK surging
during the summer of 2021.
Some scientists believe that influenza virus, new coronavirus and RSV may spread simultaneously, forming a situation of three major epidemics (tripledemic
).
In theory, the virus, which was isolated before 1956, should have had a mature vaccine available, but in practice, the development process of the RSV vaccine was not smooth
.

A bumpy road to R&D

The initial attempt to develop RSV vaccine products was a reduced- or inactivated vaccine, which was also a mature technology
at the time.
However, in a number of studies carried out before and after, the world's first clinical study, Pfizer's RSV formalin inactivated vaccine, did not play the expected role, but appeared disease enhancement (ERD), resulting in the vaccination staff after infection with RSV disease aggravation
.

Due to the death of the children tested, the FDA urgently suspended all clinical studies of RSV vaccines, and since then, the development of RSV vaccines has entered a long period
of silence.

However, in the following 60 years, scientists have not given up this research, and studies have shown that the cause of ERD may be because the vaccine activates Th2-CD4+ T cells, further leading to related cytokine-mediated pneumonia
。 Subsequently, the popularity of RSV vaccines re-emerged, but the development process was also not smooth, first the RSV F protein recombinant nanoparticle vaccine (ResVax) developed by Novavax did not reach the primary and secondary focus in the phase 3 clinical trial for the elderly, and then the clinical trial for pregnant women also failed; GSK's vaccine candidate, GSK3003891A, was discontinued
shortly after the Phase 2 clinical trial began.

The reason may be because of the peculiarities of
the RSV virus structure.
RSV is a single-stranded RNA virus, among the 8 structural proteins, fusion protein (F) and attachment protein (G) are the key to virus invasion of the human body, both of which can be ideal targets for virus development, and because G protein is more mutated and relatively unstable, F protein has become an important target
.

▲ RSV virus structure Source: Reference 2

However, F protein also has two conformations, pre-F and post-F, and pre-F is extremely unstable
.
To this end, scientists have developed techniques to modify the structure of this protein to retain neutral-sensitive epitopes while increasing protein stability
.

At present, with the further deepening of research, the further understanding of the etiology and structural biology of RSV, and the continuous development of new technologies, RSV vaccines have made many breakthroughs
.
Last year, the RSV vaccine trials of many pharmaceutical companies were successfully advanced to the late clinical stage, and showed excellent efficacy and safety, and the vaccine is just around
the corner.

Leading the company's recent progress

Internationally, the current leaders in the RSV field include Bavarian Nordic, GSK, Johnson & Johnson, Pfizer and Moderna, and several of the company's vaccine candidates are in or will be in phase 3 clinical trials; Aidi Weixin's vaccine products have entered the clinical stage, and Zhifei Biotechnology, Baike Biotechnology, Lifanda Biotechnology, as well as Watson/Lanque and CSPC Pharmaceutical Group have also mentioned the addition of RSV vaccine pipeline in public information
.

GSK

On November 3, 2022, FDA accepted the Biologics License Application (BLA) for GSK's bivalent RSV candidate GSK3844766A (RSVPreF3 OA) and granted priority review qualification
.
RSVPreF3 OA is GSK's RSV vaccine candidate for older adults and is a
combination of RSV fusion pre-F glycoprotein (RSVPreF3) and GSK's proprietary adjuvant AS01.

FDA expects to complete the review
by May 3, 2023.
If approved, GSK's RSV vaccine could be the first vaccine to protect adults over 60 years of age from lower respiratory tract disease caused by RSV infection
.

The BLA application is based on positive results from the vaccine's pivotal clinical Phase 3 trial, with data released
on October 14 last year.
The data showed that among about 25,000 subjects over 60 years of age from 17 countries, the RSV vaccine had up to 82.
6% total vaccine efficacy and more than 90% efficacy in preventing severe RSV lower respiratory tract disease, and the trial met the primary endpoint
.

In addition, GSK has developed two RSV vaccines, GSK3844766A (RSVPreF3 OA) for the elderly and GSK3888550A for maternal immunization, both vaccines containing RSVPreF3
.

Codagenix

Also on November 3, 2022, Codagenix announced that its vaccine candidate, CodaVax-RSV, for attenuated live intranasal RSV™, received FDA Fast Track designation
.
The company said CodaVax-RSV™ has a more reliable safety profile
due to its gene-edited approach to prevent wild-type regression, coupled with the intranasal route of administration, and the preclinical efficacy shown in animal models.

Pfizer

On December 8, 2022, Pfizer announced that the FDA had accepted the BLA for its bivalent RSV vaccine candidate, RSVpreF, and granted priority review status for the prevention of RSV-caused lower respiratory tract disease
in people 60 years of age and older.
RSVpreF consists of two preF proteins that optimize protection
against RSV A and B strains.
Pfizer expects the FDA to complete its review in May, meaning the vaccine could be approved at
the same time as GSK's vaccine.

The application is supported by interim positive data from the Phase 3 clinical trial AReSVi-006, which was released last August showing that the vaccine has an overall response rate of 85.
7%
for adults over 60 years of age.

At the same time, the vaccine can also be vaccinated by pregnant women to achieve newborns, and data released in November last year showed that after RSVpreF was given to mothers during pregnancy, babies could be well protected from severe lower respiratory tract diseases after birth, with a protective efficiency of 81.
8% within 90 days of birth and 69.
4%
in the first 6 months of birth.

Bavarian Nordic

The MVA-BN-RSV vaccine is a vaccine candidate developed by Bavarian Nordic, based on the company's MVA-BN platform for the prevention of RSV infection in the elderly, using five different RSV antigens to stimulate the body's broad immune response
to the A and B RSV subtypes.
Previous Phase 2 clinical trials have shown that the vaccine has shown up to 79% efficacy
in preventing symptomatic RSV infection.

In March last year, Unipharma reached a cooperation of more than $200 million with Bavarian Nordic, responsible for the development and commercialization
of the vaccine in China, South Korea and some Southeast Asian countries.
On November 14, 2022, Urui Pharma announced that the Phase 3 IND application for MVA-BN RSV vaccine was approved in China, and Phase 3 clinical trials
will be launched this year.

Ai Di Weixin

Edi Weixin's ADV110 is a protein subvaccine against RSV, consisting of purified RSV G protein as an immunogenic component and adjuvant AE011, which induces high levels of anti-G protein-specific antibodies, neutralizing antibodies against RSV infection, thereby reducing lung viral load
.

At present, the vaccine has entered Phase 2 clinical trials, and in June 2021, Edi announced that ADV110 successfully completed the first batch of subjects in Phase 2 clinical trials in Australia
.
Previous Phase 1 clinical trial results have shown that ADV110 has good safety and tolerability at low doses, high doses, as well as single and double doses, and the vast majority of subjects show a significant antibody response, reaching 90% in the low-dose group and 100%
in the high-dose group.

brief summary

Tony Wood, chief scientific officer at GSK, said: "Despite more than 60 years of research, RSV remains one of the major infectious diseases for which there is no vaccine"
.
At the end of last year, two RSV vaccines had been accepted by the FDA for BLA, and one had received fast-track designation; The monoclonal antibodies of AstraZeneca and Sanofi, although not preventive vaccines, can provide RSV immune protection without activating the immune system, and after the drug was approved in Europe last year, its BLA was accepted
by the FDA on January 6 this year.
Under this circumstance, it is inevitable that companies such as GSK and Pfizer accelerate the listing of drugs
.

2023 is destined to be a breakthrough year
for RSV vaccines.
When influenza virus, new coronavirus and RSV may be epidemic at the same time, and three major epidemics occur, RSV, a virus that affects infants and the elderly after the new crown epidemic, urgently needs effective prevention and control measures
.
Hopefully, in the new year, the RSV vaccine, which has been developed for 60 years, can write a happy ending
.

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Official website of each company