Big news! moderna announced that its mRNA RSV vaccine has been officially approved for marketing - Zhuhai Baorui Bio

Big news! moderna announced that its mRNA RSV vaccine has been officially approved for marketing

2024-06-14

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What is respiratory syncytial virus (RSV)?

Respiratory syncytial virus (RSV) belongs to the genus Normovirus under the family Pneumoviridae. It is an RNA virus with a linear single-stranded genome surrounded by a helical nucleocapsid, which in turn is enveloped by a lipoprotein membrane, giving it a spherical or filamentous appearance.

The range of this disease can extend from mild rhinitis to severe upper and lower respiratory tract disorders such as bronchiolitis and pneumonia. Although the virus can directly reveal the cellular pathology of the respiratory epithelium, in individuals with normal immune function, the immune response plays a more significant role in the pathogenicity of the disease. After the virus enters the host's body through the transmission route, it rapidly spreads to the respiratory tract and multiplies in the ciliated epithelial cells at the top.

RSV attachment glycoprotein (G) and fusion protein (F), F and G proteins induce protective neutralizing antibody responses. An effective and timely immune response against protein F can prevent severe manifestations of infection. In addition, protein F has significant interstrain conservation, making it an excellent target for potential vaccines and monoclonal antibodies (Mabs). The F protein has two conformations, namely the pre-fusion (pre-F) and post-fusion (post-F) conformations. The surface of infectious RSV is an F protein that possesses both of these conformations. After the virus infects cells, the pre-F conformation will change to the post-F conformation. Therefore, at this time, the virus surface only has the post-F conformation. Vaccines should be developed targeting the stable pre-F conformation。

susceptible/vulnerable population

Respiratory syncytial virus (RSV) belongs to the paramyxoviridae family and is one of the most important causes of lower respiratory tract diseases in infants under one year old. In addition, individuals with compromised immune, lung or heart systems, as well as the elderly, are also at high risk of RSV infection. RSV infection can cause upper respiratory tract infections and bronchiolitis, but rarely leads to pneumonia, respiratory failure, apnea and death. There are the following seven major categories of susceptible populations:

Infants under 6 months old

<2> Have underlying lung diseases(Such as bronchopulmonary dysplasia or congenital heart disease)Infants and children

<3> Infants exposed to second-hand smoke

<4> Patients with weakened immune functionFor example, patients with immune disorders or those who have recently received organ transplants

<5> Asthma patients

<6> Patients with heart and lung diseases

<7> Suffering from chronic obstructive pulmonary disease（COPD）Elderly patients

Research progress on RSV-mRNA vaccines at home and abroad

mRNA-1345 is a candidate vaccine developed by Moderna for respiratory syncytial virus (RSV) infection. It encodes an RSV protein called pre-fusion F-glycoprotein, thereby triggering an effective neutralizing antibody response. Mrna-1345 is an experimental RSV vaccine composed of a single mRNA sequence encoding a stable pre-fused F-glycoprotein.

This vaccine uses the same lipid nanoparticles (LNPs) as the Moderna COVID-19 vaccine. The F-glycoprotein is located on the surface of the virus and is necessary for infection by helping the virus enter the host cell. It exists in two states, before fusion and after fusion. The pre-fusion conformation is an important target for potent neutralizing antibodies and is highly conserved in both the RSVA and RSV-B subtypes. Recently, Moderna reported the interim results of an ongoing Phase 1 study, which evaluated the tolerance, reactivity and immunogenicity of mRNA-1345 in children, young people, the elderly and women of childbearing age.

The results showed that the vaccine had good tolerance at all dose levels in the trial. A phase 2/3 study of the mRNA-1345 vaccine (NCT05127434) in adults aged 60 and above is currently underway to evaluate the safety and tolerability of the mRNA-1345 vaccine and to demonstrate that from 14 days to 12 months after injection, compared with placebo, The efficacy of a single dose of mRNA-1345 vaccine in preventing the first onset of RSV-associated lower respiratory tract disease (RSV-LRTD). This study is planned to be conducted in two placebo-controlled phases, namely a Phase 2 study with 400 to 2,000 participants and a Phase 3 study with over 30,000 participants.

The main purpose of this study is to evaluate the safety and efficacy of the vaccine. The safety endpoints include monitoring the incidence of adverse reactions, adverse events, serious adverse events, and adverse events of special concern among the participants. The primary efficacy endpoints included the vaccine efficacy (VE) of mRNA-1345 in preventing the first episode of RSV-LRTD from 14 days to 12 months after injection. This research began in November 2021 and is expected to be completed in November 2024 (NCT05127434).

-- Frontier Progress of Domestic RSV-mRNA Vaccines --

Advantages of mRNA vaccines

mRNA vaccines generally refer to mRNA vaccines for the novel coronavirus, which are used to prevent novel coronavirus infection. The types of vaccines also include inactivated vaccines, attenuated live vaccines, DNA vaccines, etc. Compared with other vaccines, mRNA vaccines have the advantages of safety, high efficiency, and easy production, but they also have disadvantages such as strong immune response and high storage conditions。

Advantages

"1. Safety

The principle of the mRNA novel coronavirus vaccine is to introduce the virus mRNA as an antigen into the body, stimulating the body to produce an immune response. Due to the relatively low risk of infection.

2. "Efficient"

mRNA vaccines can achieve the purpose of preventing viral infection through dual immunity of humoral and T-cells, and can also combat viral mutations。

3. Easy to produce

mRNA vaccines are technically challenging, but compared with inactivated virus vaccines that require a series of production processes such as cell culture, virus extraction and inactivation, the production process is simple and can even be directly transcribed in vitro without using cells.

4. Others

mRNA vaccines have high immunogenicity and do not need to act in combination with other vaccine adjuvants, reducing possible side effects caused by other substances.

Disadvantage

1. Strong immune response

Due to the strong antigenicity of mRNA vaccines for the novel coronavirus, they may trigger a strong immune response in the human body, causing discomfort such as inflammation, and may also lead to local irritation or allergies.

2. High storage conditions

It needs to be stored at a lower temperature and away from light. During the transportation and storage in clinical Settings, a large amount of materials will be consumed。

mRNA drug delivery method

Biori

Some researchers have found that apolipoprotein E (ApoE) adsorption is an important reason for mediating the liver targeting of lipid nanoparticles. The current formulations of LNP delivery systems used for mRNA vaccines are all liver-targeted. By altering the four lipid components of the LNP formulation or adding additional auxiliary lipids, the regulation of the "protein crown" component can be achieved to deliver LNP to the lungs, spleen and liver.

The active targeted delivery strategy achieves the receptor-specific recognition and binding of LNP to tissues or cells by adding targeted molecules such as peptides, antibodies and antibody fragments, and nucleic acid aptamers on the surface of LNP, thereby increasing the effective delivery of mRNA to specific tissues or cells and reducing toxicity。

The End

References

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