HKU confirms that some flu vaccines cause a stronger immune response in older adults

A new study led by scholars at the School of Public Health, LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and The United States Centers for Disease Control and Prevention provides more encouraging evidence that certain specially formulated flu vaccines may offer people aged 65 or above better protection than standard-dose flu vaccines. The findings are now published in the journal Clinical Infectious Diseases (link to publication).

People aged 65 or above are generally considered at high risk of developing serious flu complications, yet vaccines may not work as well for them as they do in younger people. There are at least three relatively new influenza vaccine options that may improve vaccine protection for older adults, and this is the first study to directly compare the antibody responses of these newer vaccine options with standard flu vaccines among the same group of older adults during the same influenza season. These new vaccines are available commercially elsewhere such as the United States, the United Kingdom and Australia, but are not yet available in Hong Kong.


During most influenza seasons, people aged 65 years or above account for the majority of flu hospitalisations and deaths. In Hong Kong, around 95 percent of seasonal flu-related deaths and 57 percent of seasonal flu-related hospitalisations occurred among people aged 65 years or above. This is partly because human immune defence becomes weaker with age, thus older adults are at high risk of developing serious complications from flu compared with young, healthy adults. The weakened immune system can also imply that older people do not respond as well to flu vaccination.

Research method

To assess whether next-generation influenza vaccines could provide better protection in older adults, this study randomly assigned older adults in Hong Kong to receive either a standard 4-component inactivated flu vaccine, or one of three other “enhanced” inactivated flu vaccine options specially designed to improve vaccine protection among older adults:

A high-dose 3-component flu vaccine that contains four times the amount of antigen as a regular-dose flu vaccine, which in turn elicits a stronger response to vaccination;
A standard-dose 3-component flu vaccine but also contains a specially formulated adjuvant (MF59), which is an ingredient that may provide broader response in the face of antigenic drift of circulating viruses, and;
A 4-component recombinant hemagglutinin (HA) vaccine that involves cell-based rather than egg-based vaccine manufacturing process and uses recombinant technology in producing the influenza HA antigens, which provides a better match between the vaccine and circulating virus. This vaccine also contains three times the amount of antigen as a regular-dose flu vaccine.
Although there is some evidence that these three relatively new vaccines are able to improve protection for older adults, no study, until this one, has directly compared the immune responses by these vaccines in the same year, with the same components, in the same population.

Research findings and significance

The study found that all three of the “enhanced” vaccines produced an improved immune response against influenza A(H1N1) and A(H3N2) compared to the standard-dose vaccine. For example, older adults who received an enhanced vaccine had a 4.2- to 4.7-fold increase in antibodies to the egg-like A(H3N2) component of the vaccine following vaccination, compared to a 3.4-fold increase among those who received a standard-dose vaccine. Compared to other enhanced vaccines, older adults who received the recombinant-HA vaccine had a significantly higher antibody response to a cell-like A(H3N2) strain that was similar to the A(H3N2) viruses that circulated locally. On the other hand, immune responses to the B/Victoria vaccine component, which was the selected influenza B vaccine component included in all the four vaccine options, were similar across vaccines, with the exception of higher post-vaccination antibodies among those who received high-dose vaccine.

The improved antibody response in older adults observed with all three enhanced vaccines is consistent with findings from previous studies that looked at these vaccines in an individual basis. Although increased antibody response following vaccination does not guarantee better clinical protection against influenza illness, the improved immune response against the A(H3N2) viruses by the enhanced vaccines might support that enhanced vaccines would be particularly useful for older adults, especially under the context that influenza A(H3N2) virus has been associated with higher mortality and hospitalisation rates in adults aged 65 years or above in recent influenza seasons.

Nevertheless, further studies are needed to directly compare the value of each vaccine in preventing clinical flu illness. This study lays the groundwork for future efficacy trials and effectiveness studies on enhanced vaccines in older adults, and helps in planning for those more definitive evaluations and anticipating the differences in efficacy/effectiveness that might plausibly be expected.

Professor Benjamin Cowling, Principal Investigator of this study and Division Head of Epidemiology and Biostatistics of School of Public Health, HKUMed, said, “This study found that the new enhanced influenza vaccines can provide improved protection against influenza for older adults, and should be considered for use here in Hong Kong.”

About the research team

The research was conducted by a team led by Professor Benjamin Cowling, Professor of the School of Public Health, HKUMed, in collaboration with a team from the Influenza Division of the United States Centers for Disease Control and Prevention led by Dr Mark Thompson and Dr Danielle Iuliano. The project was funded by collaborative agreement with the United States Centers for Disease Control and Prevention.