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A new single-dose influenza vaccine may produce a longer lasting immune response than the current stability of influenza vaccines.
Immunization with replication competent recombinant vectors provides exposure to the antigens encoded by the transgene in the context of inflammation, which could be a driver for more potent and longer lasting protection compared to non-replicating vaccines.
A team, led by Kenta Matsuda, HIV Specific Immunity Section of the Immunoregulation Laboratory, National Institutes of Allergy and Infectious Diseases, NIH, tested a replicating type 4 adenovirus encoding hemagglutinin of the virus. H5 influenza (Ad4-H5-Vtn) given by an oral capsule or by a tonsil swab or nasal spray to better understand the characteristics of a replicating vaccine that drives this response.
In the study, researchers measured viral excretion from the nose, mouth, and rectum using a polymerase chain reaction (PCR) test and cultures. They also measured serum antibodies by a pseudovirus entry inhibition test (PVEI), microneutralization (MN) and hemagglutinin inhibition (HAI).
Different types of vaccines
The study included 28 participants who received the vaccine intranasally, 10 people who received the vaccine as an oral capsule, and 25 people who received the vaccine as a tonsil swab. The patient population consisted of healthy males and non-pregnant females aged 18 to 49 years.
People who received the vaccine intranasally or by a tonsil swab had significantly higher levels of H5 specific neutralizing antibodies than the group who received the vaccine orally.
The researchers found that ad4-H5-Vtn DNA was excreted by most immune volunteers from the upper respiratory tract (URT) for 2 to 4 weeks. However, grown from only 60% of participants with a median length of 1 day.
In addition, the Ad4-H5-Vtn vaccine induced increases in H5 specific CD4 + and CD8 + T lymphocytes in peripheral blood and IgG and IgA in nasal, cervical and rectal secretions.
The researchers also found that upper respiratory tract immunizations induced high levels of serum neutralizing anti-H5 antibodies, which remained stable at week 26 of the study, while the duration of viral shedding correlated. with the magnitude of the neutralizing antibody response at week 26.
Overall, the adverse events were mild, with peak neutralizing antibody titer associated with the frequency or duration of the adverse events. Researchers believe serum neutralizing antibody titers could be increased to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant or inactivated H5N1 fractionated H5 vaccine.
Future hope
“Ad4 replication delivered to URT results in prolonged antigen exposure, promotes long-lasting systemic and mucosal immunity, and provides a promising platform for induction of immunity against viral surface glycoprotein targets. », Wrote the authors.
The researchers said that replication competent vector vaccines are advantageous because they can express viral proteins at higher levels and for longer durations.
The researchers also said the vaccination platform may be adaptable for use against other viruses, such as HIV and SARS-CoV-2.
The study “A replication-competent adenovirus vector influenza vaccine induces long-lasting systemic and mucosal immunity”, has been published online in The Journal of Clinical Investigation.
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