A novel concept for one universal flu vaccine candidate has now passed its first test in a small clinical trial. The Phase I results are in and strong functional antibodies have been found to last more than a year after the vaccination.
The influenza viruses are segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. Two glycoproteins facilitate the entry into host cells - namely hemagglutinin (HA) and neuraminidase (NA).
There are three main types of influenza viruses., A, B & C.
Influenza A viruses gets subdivided based on their HA and NA proteins. Three HA subtypes (H1, H2, H3) and two NA subtypes (N1, N2) have be shown to cause widespread influenza transmission in humans.
The HA molecule contains two regions - the head and a stalk. The head is more prominent than the stalk, and antibodies to the head of the HA molecule have been shown to neutralize viral infectivity.
Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or the head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does mutate frequently, which allows new viral strains to dodge any immune memory and forces flu vaccine makers to prepare new formulations each year, with updated HAs.
The Stalk of the HA, however, remains more conserved and some clever researchers thought that a vaccine that targets the HA Stalk might offer protection independent of antigenic drift or shift. Studies did show that people who have been exposed to an influenza strain and developed antibodies to the stalk can ward off a wide variety of other strains. Thus the Universal Flu Vaccine candidate was developed that uses the HA Stalk as the target.
Targeting the stalk is harder than it sounds, because immune memory cells built up over a lifetime of flu infections react so strongly to the conserved region of HA’s head that this response overrides production of antibodies against the stalk. Some researchers have tried to make flu vaccines that only contain HA’s stalk, but this fragment is highly unstable. To get around this problem, Florian Krammer (Virologist, Team Lead- Icahn School of Medicine at Mount Sinai, NewYork) and colleagues made what they call chimeric HAs, which link the protein’s conserved stalk to unusual heads that are entirely new to the human immune system and don’t trigger a person’s immune memory. Only low levels of head antibodies are produced, allowing a strong new immune response to stalk to dominate. In essence, the head of the chimera is only there to stabilize the stalk.
It will take at least another two years to develop this vaccine. However there are several different groups working on the universal flu vaccine.
Note - Chimera in Greek mythology is a hybrid mythical creature depicted as a Lion with a head of a goat at the back and a tail with a snake head. In general Chimera is a fictional creature with parts taken from various animals .
The influenza viruses are segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. Two glycoproteins facilitate the entry into host cells - namely hemagglutinin (HA) and neuraminidase (NA).
There are three main types of influenza viruses., A, B & C.
Influenza A viruses gets subdivided based on their HA and NA proteins. Three HA subtypes (H1, H2, H3) and two NA subtypes (N1, N2) have be shown to cause widespread influenza transmission in humans.
The HA molecule contains two regions - the head and a stalk. The head is more prominent than the stalk, and antibodies to the head of the HA molecule have been shown to neutralize viral infectivity.
Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or the head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does mutate frequently, which allows new viral strains to dodge any immune memory and forces flu vaccine makers to prepare new formulations each year, with updated HAs.
The Stalk of the HA, however, remains more conserved and some clever researchers thought that a vaccine that targets the HA Stalk might offer protection independent of antigenic drift or shift. Studies did show that people who have been exposed to an influenza strain and developed antibodies to the stalk can ward off a wide variety of other strains. Thus the Universal Flu Vaccine candidate was developed that uses the HA Stalk as the target.
Targeting the stalk is harder than it sounds, because immune memory cells built up over a lifetime of flu infections react so strongly to the conserved region of HA’s head that this response overrides production of antibodies against the stalk. Some researchers have tried to make flu vaccines that only contain HA’s stalk, but this fragment is highly unstable. To get around this problem, Florian Krammer (Virologist, Team Lead- Icahn School of Medicine at Mount Sinai, NewYork) and colleagues made what they call chimeric HAs, which link the protein’s conserved stalk to unusual heads that are entirely new to the human immune system and don’t trigger a person’s immune memory. Only low levels of head antibodies are produced, allowing a strong new immune response to stalk to dominate. In essence, the head of the chimera is only there to stabilize the stalk.
It will take at least another two years to develop this vaccine. However there are several different groups working on the universal flu vaccine.
Note - Chimera in Greek mythology is a hybrid mythical creature depicted as a Lion with a head of a goat at the back and a tail with a snake head. In general Chimera is a fictional creature with parts taken from various animals .
