The Future of Influenza Vaccine Design

The impact of influenza can only be reduced through a vaccine. Today, the U.S. has only approved the use of inactivated influenza virus vaccines, and to be effective, these have to contain an H1N1, and H3N2, and a B virus component. In the past, at least one of these components had to be modified due to antigenic drift of the strain circulating the human population.

Vaccines are prepared by growing viral strains in embryonated eggs, and then the virus is purified and turned noninfectious through chemical inactivation. The influenza vaccines available today are effective depending on the antigenic ‘match’ of the circulating viruses with the strains used for vaccination, the person’s age, and his or her immune status.

Here’s what is expected in the future; ask your pharmaceutical consultant for further details:

1. Cold-adapted influenza virus vaccine

This type of live vaccine has been used successfully in Russia to protect millions of children. The U.S. has been trying to develop such a vaccine for over 20 years, but the license has not been approved yet.

There are several important advantages here:

– Live-virus vaccines can be administered through nasal spray, which is easier and less costly than the intramuscular option.

– These can induce local neutralizing immunity and cell mediated immune responses, which could result in a longer-lasting and better cross-protective immunity.

– Overall protection may improve for certain age groups, for example, kids 6 months to 9 years of age, with evidence of a massive reduction in secondary bacterial infections causing otitis media.

The more live influenza virus vaccines are used, the more benefits, risks, and economic consequences of this approach will be known.

2. Genetically engineered live influenza virus vaccines

The introduction of techniques to engineer site-specific changes in the genomes of negative-strand RNA viruses has allowed the consideration of new vaccine approaches. It is possible now to create strains with unique properties that lead to reduction.

3. Live influenza virus vaccine candidates expressing altered NS1 genes

Now it is possible to rescue influenza virus vaccine candidates from cells transfected with plasmids. This allows for the engineering of deletions in genomes of influenza viruses for better stability.

4. Use of replication-defective influenza viruses as vaccine candidates

This is a promising approach, the construction of virus particles that undergo only a single cycle of replication. These induce a protective antibody response and stimulate a strong cell-mediated immune response without allowing the replication of infectious virus.

5. DNA vaccination

This involves the administration of plasmid DNA encoding one or more of the influenza virus proteins. Studies have been limited to animal samples with very promising results; however, this type of vaccine may be better for diseases like AIDS. Further studies may present a universal approach to generating protective humoral and cell-mediated responses to different foreign antigens, resulting in the development of effective vaccines.

6. New adjuvant approaches

Current influenza virus vaccines are administered by intramuscular injection. To improve their immunogenicity, liposome-like preparations have been developed, which contain cholesterol and viral particles that are very effective in mice when delivered subcutaneously or in intranasal form. More tests are needed to confirm how it will work in humans.

7. Universal vaccine

This has been the focus of increased attention due to the current necessity to develop a new vaccine every year given the influenza virus’ continuous antigenic change. Even though some virus components are more conserved than others, a good approach to a universal vaccine based on these conserved elements is still pending, because these are minor antigens, and thus, are less immunogenic and less likely to create a protective response.