RSV Vaccine Production Methods
The RSV vaccines currently available are produced using recombinant protein technology, with two main types available in Portugal: a recombinant RSV pre-fusion F protein adjuvanted with AS01E (RSVPreF3) and a recombinant bivalent RSV-A and RSV-B pre-fusion F protein (RSVpreF). 1
Current RSV Vaccine Production Technologies
The stabilization of the RSV-F glycoprotein in the prefusion (preF) conformation was a key breakthrough for efficient RSV vaccine design, as this is the primary target of RSV-neutralizing antibodies 2
Two protein subunit vaccines (GSK's Arexvy/RSVPreF3 and Pfizer's Abrysvo/RSVpreF) and one mRNA RSV vaccine (Moderna's mRESVIA) have been developed using this approach 2
The recombinant RSVPreF3 vaccine contains the RSV pre-fusion F protein adjuvanted with AS01E, while the RSVpreF vaccine contains recombinant bivalent RSV-A and RSV-B pre-fusion F proteins 1
Historical RSV Vaccine Development Approaches
Early efforts to develop RSV vaccines used classic methods of serial cold-passage and chemical mutagenesis to create live-attenuated vaccines 3
More recent approaches have utilized reverse genetics to derive attenuated derivatives of wild-type RSV and to develop parainfluenza vaccine vectors that express RSV surface glycoproteins 3
Live-attenuated RSV vaccines were historically considered advantageous for infants and young children because they: 1) do not cause vaccine-associated enhanced RSV disease; 2) broadly stimulate innate, humoral, and cellular immunity; 3) can be delivered intranasally; and 4) can replicate in the upper respiratory tract despite the presence of maternal antibodies 3
Alternative Production Technologies
Self-amplifying RNA (saRNA) vaccine platforms represent an emerging technology that holds promise for eliciting both humoral and cellular immune responses against RSV 4
The saRNA vaccine platform encodes a stabilized form of the RSV fusion protein within lipid nanoparticles (LNPs) 4
Studies in non-human primates have shown that saRNA vaccines can induce RSV neutralizing antibodies and cellular responses in both RSV-naïve and previously infected subjects 4
Challenges in RSV Vaccine Production
Several obstacles have historically complicated RSV vaccine development, including:
- The need to immunize very young infants who may respond inadequately to vaccination
- The existence of two antigenically distinct RSV groups (A and B)
- The history of disease enhancement following administration of a formalin-inactivated vaccine in the 1960s 5
The lack of an absolute correlate of protection and the need for selecting appropriate virus attenuation and antigen-adjuvant combinations contributed to delayed vaccine production 2
Vaccine Types for Different Populations
Different vaccine types may be optimal for different populations:
- Protein subunit and nanoparticle vaccines appear most promising for pregnant women and the elderly
- Live-attenuated or vector-based vaccines may be more suitable for the pediatric population 6
The current RSV vaccines are administered as a single intramuscular dose, preferably between September and November before or early in the RSV season 7
The vaccines can be co-administered with seasonal influenza vaccine at different injection sites 7, 8
Future Directions
Ongoing studies on RSV vaccines may justify extending current vaccination recommendations in the future 1
Combination vaccines conferring protection against several respiratory illnesses in one dose could help improve vaccine acceptance and coverage rates in older adults 2
Further evaluation of vaccine efficacy and safety in immunocompromised patients, frail elderly subjects, and young infants is necessary, as these populations were under-represented in pivotal clinical trials 2