New Combination Vaccines on the Horizon: COVID-19 and Influenza Bivalent Vaccine Expected to Launch in 2025–2026
SINOVAC
Vaccine Research, Production, and Sales
BioNTech
Developer of Novel Biologics
Novavax
Innovative Vaccine Developer
Pfizer
Pharmaceutical R&D Developer
Data from the China CDC's weekly report on the novel coronavirus shows that over the past year, China has continued to experience concurrent outbreaks of both COVID-19 and influenza. Moreover, the prevalence of COVID-19 does not exhibit the distinct seasonality characteristic of influenza. However, both the vaccination campaign and research development for COVID-19 in China have nearly come to a standstill.
In terms of the convenience of developing a combined COVID-19 & influenza vaccine, only SINOVAC and China National Biotec Group (CNBG) in China have reserves of both vaccine products. However, neither company’s official website indicates plans to develop a combined vaccine.
01/The Value of Combined Vaccines in Adult Disease Prevention and Control
In vaccine inoculationAndA Game-Changer in Terms of Coverage, but only if a combination of multiple antigens is used.Correct.——PreviousUnited StatesCDC、WHOVaccine PolicyExpertKathleen Neuzil。
"Adults' fear of needles may be a serious issue beyond our understanding," said Robert Hopkins, an internist at the University of Arkansas for Medical Sciences.Moreover, NPJ Vaccines pointed out that the acceptance of simultaneous administration of multiple vaccines among American adults was not as expected.
As early as 1948, the combined vaccine for diphtheria, tetanus, and pertussis was first put into use, significantly increasing immunization coverage and minimizing the incidence rate among infants and young children.
Similarly, the application of combination vaccines in China has increased the capacity for immunization program vaccines and the vaccination rate of some non-immunization program vaccines for children under one year old. In terms of adult vaccine applications, convenience of vaccination and time costs are also key factors limiting the improvement of adult vaccination rates.
02/
The First New Adult Combination Vaccine Is On the Way
The pandemic and the application of new technologies have provided opportunities for the development of new combination vaccines for adults. The first new combination vaccine for adults is likely to target COVID-19 and influenza, both of which are now recommended annually for adults and children aged 6 months and older.
Pfizer, BioNTech, Moderna, and Novavax are all developing and testing this combination vaccine. Among them, Pfizer, BioNTech, and Moderna have completed Phase 3 trials of their mRNA vaccines targeting COVID-19 and influenza, but have not yet reported the results. These companies stated that if the trial results are encouraging, they are expected to launch this combination vaccine in the fall of 2025.
Image source: Internet
On May 10, Novavax, Inc. and Sanofi announced an agreement to develop a new combination vaccine using Novavax's COVID-19 vaccine and Sanofi's influenza vaccine.
Novavax, Inc. (the manufacturer providing the COVID-19 vaccine in the United States) plans to launch the Phase III trial of its combined vaccine later this year. The vaccine uses fragments of viral proteins to stimulate the immune system and is expected to be available in the fall of 2026.
Another adult combination vaccine expected to enter Phase III clinical trials this year targets two other common but under-recognized respiratory viral infections—RSV and HMPV (human metapneumovirus). The former is often mistakenly considered in clinical settings to impose a disease burden only on children, while the latter is rarely known.
Image source: Internet
Serological studies have found that HMPV was first reported in 2001 but has been circulating since the 1950s, only it had never been identified. HMPV can cause respiratory illnesses in people of all ages in temperate climate regions and is most active in late winter and spring. Currently, there is no vaccine specifically targeting HMPV alone, but in February this year, AstraZeneca acquired a company named Icosavax, which developed a combined RSV and HMPV vaccine using a virus-like particle (VLP) platform, named IVX-A12.
03/
Technical Challenges in the Development of Combined Vaccines for Adults
Current vaccines for preventing respiratory diseases only address multivalent forms — they target a single formulation for multiple strains of the same pathogen (such as seasonal flu, pneumonia, COVID-19, RSV, etc.), rather than targeting multiple unrelated infectious pathogens (e.g., a combined COVID-19 & influenza vaccine).
Neuzil pointed out that it is simpler to combine pediatric vaccines for simultaneous administration—they follow similar immunization schedules for the same age group, so the combination works well and is reasonable.
However, the development of combined vaccines for adults needs to match the complex specific target populations, vaccination schedules, and frequencies faced by multiple single vaccines. Therefore, researchers cannot simply combine or mix any two vaccines.
For example, it is unreasonable to mix the HPV vaccine with the shingles vaccine because the former is only applicable to people under 45, while the latter is routinely recommended for those aged 50 or above. It is also unwise to combine the tetanus vaccine with the flu vaccine, as the former is administered every 10 years, whereas the latter is given annually.
04/
New Link Vaccine May Help Increase COVID-19 Vaccination Rates
Other countries have never relaxed their guard against COVID-19, but the significant drop in trust in COVID-19 vaccines has led to persistently disappointing vaccination rates for new formulations.
A 2022 systematic review and meta-analysis concluded that co-administration of the influenza vaccine and the COVID-19 vaccine could potentially increase the latter's vaccination rate, primarily because many people are already accustomed to receiving the flu vaccine annually.
Currently, one benefit of recommending co-administration of the COVID-19 vaccine with the seasonal flu vaccine each autumn is that it helps normalize COVID-19 vaccination and increase coverage rates.
Image source: Internet
Despite the CDC's recommendation in the past two flu seasons that the two vaccines can be administered simultaneously, the vaccination rate for COVID-19 remains much lower than that for the flu, possibly due to the higher level of public trust in the flu vaccine.
As of May, the vaccination coverage rates for COVID-19 and influenza vaccines among U.S. adults aged ≥18 were 22.5% and 48.4%, respectively; among children and adolescents aged 6 months to 17 years, the coverage rates were 14.1% and 52.9%, respectively. In all age groups, the vaccination coverage for influenza was more than twice that for COVID-19.
05/
Other Issues Facing the New Combined Adult Vaccine
COVID-19 and influenza both peak in winter, but so far, COVID-19 has not disappeared in spring and summer like the influenza virus, and people can be infected with COVID-19 throughout the year. The prevalent strains of influenza change every year, making it necessary to update the vaccine annually. However, the evolution of SARS-CoV-2 may eventually slow down, potentially eliminating the need to update the COVID-19 vaccine every year.
In addition, new combination vaccines need to address the potential issue of reduced immune response. Although co-administration of influenza and COVID-19 vaccines appears not to reduce, and may even enhance, efficacy, the situation could change if they are integrated into a combination vaccine.
For example, when Merck added the varicella vaccine to the MMR vaccine to create a quadrivalent vaccine, it was necessary to use a higher dose of the varicella vaccine than the monovalent vaccine in order to achieve a similar immune response.
Novavax to Increase SARS-CoV-2 Antigen to 35ug in Phase III Clinical Trial, Seven Times the Dose of a Single Vaccine. Additionally, Novavax Tested the Antigen Levels of Three Influenza Strains Combined with the COVID-19 Vaccine and Determined Optimal Immunogenicity at 30ug, 45ug, and 60ug for Each Strain.
JAMA.Published online May 17, 2024. doi:10.1001/jama.2024.7370
