There are many new and improved vaccines for Covid-19, influenza (flu), RSV and other diseases1-12. At the same time, recent data has shown that antibodies persist through six months after a second dose of the original Covid-19 vaccines that used mRNA technology13-14. This technology is used to make vaccines for preventing influenza, RSV and other diseases, including cancer15. The vaccines against influenza and RSV are especially important for the very young, elderly and people with respiratory diseases such as asthma.
The original mRNA vaccines made by Moderna/Lonza (mRNA-1273) and Pfizer/BioNTech (BNT162b2 or Comirnaty) target the original type of SARS-CoV-2 virus that causes Covid-19. The vaccines contain a self-replicating mRNA that encodes the entire spike (S) protein that the SARS-CoV-2 virus uses to bind to ACE-2 receptors on the membranes of host cells in the nose, lungs, heart and many other parts of the body. Both require a booster shot, 30 days after the first one. The mRNA in both vaccines has a modified nucleic acid (1-methyl-pseudouridine) that increases the translation of mRNA into the S protein and helps avoid harmful over-activation of the innate immune system. Both vaccines are encapsulated with lipid nanoparticles and were over 90% effective in clinical trials.
Since then, the SARS-CoV-2 virus has mutated many times to produce new variants, such as alpha, beta, gamma, delta and omicron16. Currently, the omicron subvariant BA.5 is the most widespread17. So, newer bivalent vaccines have been developed. They contain not only the original form of the vaccine, but also a form that targets the spike protein of the omicron variant2-5. For example, a 50-μg bivalent vaccine called mRNA1273.214 (25 μg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) was compared with the previously authorized 50-μg mRNA-1273 booster3. The mRNA-1273.214 or mRNA-1273 vaccines were given as a second booster in adults who had previously received a two-dose (100-μg) primary series and a first booster (50-μg) dose of mRNA-1273 (at least 3 months earlier). The bivalent omicron-containing vaccine mRNA-1273.214 produced neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without any safety concerns3.
Pfizer/BioNTech has a bivalent vaccine called Pfizer-BioNTech COVID-19 Vaccine, Bivalent. It contains both the original Comirnaty and omicron BA.4/5.There are two bivalent candidates from Moderna/Lonza: mRNA-1273.214, which targets the BA.1 subvariant of omicron, and mRNA 1273.222, which targets the BA.5 subvariant. A conditional authorization for mRNA-1273.214 has already been granted by the United Kingdom’s Medicines and Healthcare products Regulatory Agency.
However, Moderna/Lonza and Pfizer/BioNTech vaccines are not always as successful in being able to block the transmission chain, prevent breakthrough infections, and provide protection against severe disease6. They don’t provide respiratory mucosal immunity against omicron in some people. They often fail to prevent the chronic post-Covid-19 syndrome, also known as long Covid and persistent post-Covid syndrome (PPCS) 18,19.
So, nasal vaccine candidates have been developed. They can produce mucosal immunity, as well as increase the circulating immunity achieved through previous intramuscular injections of mRNA vaccines. A study showed that mucosal immunity could be produced with a nasal vaccine in mice20. The National Medical Products Administration of China recently approved a nasal vaccine called Convidecia Air. It is made by CanSino Biologics, a Chinese pharmaceutical company. Another nasal vaccine called BBV154 was developed at Washington University in St. Louis, USA21. The nasal delivery system was designed to be cost-effective and it can be stored in a refrigerator. It is briefly inhaled, a major advantage to the many people who prefer to avoid needles. Moreover, the vaccine can be easily updated as new variants emerge. It is approved in India for emergency use. Precision Virologics has optioned rights for Europe, USA and Japan, while Bharat Biotech has retained rights for all other markets. Emergency use authorization granted in India. Bharat Biotech can manufacture 150 million doses per year. They will also be sent to Sri Lanka, Mongolia, Myanmar, Bahrain, Oman, the Philippines, Maldives and Mauritius.
Covid-19 vaccinations could save thousands of lives and billions of dollars this winter22. A recent analysis estimated that if enough people in the USA get their booster vaccines by the end of the year, about 90,000 deaths by Covid-19 could be prevented this fall and winter. However, if booster vaccinations continue at their current pace, the USA could see a peak of more than 1,000 deaths by Covid-19 per day this winter22.
Vaccinations can also prevent deaths caused by influenza and RSV23,24. RSV is a common respiratory virus that usually causes mild, cold-like symptoms25. Most people recover in a week or two, but RSV can be serious, especially for infants and older adults. RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia (infection of the lungs) in children younger than 1 year of age in the USA25. About 177,000 adults are hospitalized and 14,000 die by RSV annually23. Over 57,000 hospitalizations, 500,000 emergency department visits and 1.5 million outpatient clinic visits among children <5 years of age are attributed to RSV each year in the USA23. It was estimated that lower respiratory tract infections (LRTI) associated with RSV accounted for between 94,600 and 149,400 deaths worldwide26. In addition, 33 million RSV‐associated LRTIs resulted in 3.2 million hospital admissions.
There are no licensed vaccines for RSV, but Pfizer/BioNTech and Moderna/Lonza have vaccine candidates that have been successful in clinical trials. A clinical trial showed that Pfizer’s RSVpreF vaccine was safe and effective when given to women at 24 through 36 weeks’ gestation27. It was also safe and effective when given together with the tetanus, diphtheria, and acellular pertussis vaccine, Tdap, to nonpregnant women 18‒49 years of age28. Moderna/Lonza’s mRNA-1345 vaccine is being tested in children, younger adults and adults ≥50 years of age2929. Its safety and efficacy when given with their mRNA-1273.214 Covid-19 vaccine and in combination with a seasonal influenza vaccine (Afluria® Quadrivalent) 29.
On the other hand, there are several licensed vaccines against influenza, which kill about 5943 people (1.8 per 100,000) 24. The death toll is so high because only about 70.8% of adults over 65 and 52.5% of children aged 6 months to 17 years have received a flu vaccine in the past 12 months. There are five egg-based vaccines, one based on cell culture, one based on eggs with an adjuvant added, and one recombinant hemagglutinin (HA) vaccine. Three of these are recommended for people over 65: Fluzone high-dose quadrivalent, Flublok recombinant and Fluad quadrivalent with adjuvant. As in previous years, the composition of the vaccine has been changed, based on the emergence of new strains or types of influenza viruses that emerge30. Vaccine strains for the 2022–23 influenza vaccines were selected by the Food and Drug Administration’s Vaccines and Related Biologic Products Advisory Committee based on WHO’s recommended Northern Hemisphere 2022–23 influenza vaccine composition31. No changes were made to the components that targeted the A(H1N1)pdm09 and B/Yamagata subtype of the virus. The recommended A(H3N2) and B/Victoria components were changed.
In the meantime, Moderna/Lonza and Pfizer/BioNTech have developed and are testing mRNA vaccines against influenza32; the mRNA does not intermingle with the host genome. It is simply a safe carrier of information. Different mRNAs can be designed and manufactured much faster than other types of vaccines. This enables the development of a broad range of vaccines for other major infectious diseases. The mRNA is encapsulated in a specific liposome and complexing agent. The suitable liposome and complexing agent enhance the cellular uptake of the mRNA. This enables efficient translation into the desired immunogenic protein in the cytoplasm of the host cell. The liposomes also minimize mRNA degradation before reaching the cytoplasm of the cell. So, mRNA vaccines are in clinical trials for contraception and treating several types of cancer, cystic fibrosis, obesity, several metabolic diseases (such as diabetes and phenylketonuria), heart failure, endometriosis, lupus, inflammatory bowel disease, atopic dermatitis, and preventing infections by endemic human coronaviruses, CMV, zika, RSV, influenza, rabies, EBV (infectious mononucleosis), HSV, VZV, HIV, chikungunya and hMPV (Human metapneumovirus)32.
So, we may see many more diseases being prevented and cured by these vaccines. Still, ignorance and politics cause many people to fear vaccines instead of the diseases that they prevent. The unvaccinated continue to die needlessly.
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3 Chalkias, S. et al. A bivalent omicron-containing booster vaccine against Covid-19. The New England Journal of Medicine, 16 Sept. 2022.
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21 Sharun, K. et al. India’s role in COVID-19 vaccine diplomacy. International Journal of Travel Medicine, 2021.
22 Fitzpatrick, M.C. et al. A Fall COVID-19 booster campaign could save thousands of lives, billions of dollars. The Commonwealth Fund, 6 Oct. 2022.
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