Participants who received the vaccine intranasally or through the tonsillar swab had significantly higher H5-specific neutralizing antibody levels than the group that received the vaccine orally.
A new single-dose influenza vaccine could yield a more durable immune response than the current stable of influenza vaccines.
Immunization with replication-competent recombinant vectors provides exposure to transgene-encoded antigens in the context of inflammation, which could be a driver for more potent and durable protection compared to non-replicating vaccines.
A team, led by Kenta Matsuda, HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, NIH, tested a replication-competent adenovirus type 4 encoding influenza virus H5 hemagglutinin (Ad4-H5-Vtn) administered by an oral capsule or through a tonsillar swab or nasal spray to better understand the features of a replicating vaccine that drives this response.
In the study, the researchers measured viral shedding 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 assay (PVEI), microneutralization (MN), and hemagglutinin inhibition (HAI).
Different Vaccine Types
The study included 28 participants who received the vaccine intranasally, 10 individuals who received the vaccine as an oral capsule, and 25 individuals who received the vaccine as a tonsillar swab. The patient population was health men and non-pregnant women between 18-49 years old.
The individuals who received the vaccine intranasally or through the tonsillar swab had significantly higher H5-specific neutralizing antibody levels than the group that received the vaccine orally.
The researchers found ad4-H5-Vtn DNA was shed from most upper respiratory tract (URT)-immunized volunteers for 2-4 weeks. However, cultured from only 60% of participants with a median duration of 1 day.
In addition, the Ad4-H5-Vtn vaccine induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood and IgG and IgA in nasal, cervical and rectal secretions.
The investigators also found upper respiratory tract immunizations induced high levels of serum neutralizing antibodies to H5, which remained stable at week 26 of the study, while the duration of viral shedding correlated with the magnitude of the neutralizing antibodies response at week 26.
Overall, adverse events were mild, with peak neutralizing antibodies titer associated with adverse event frequency or duration. The researchers believe serum neutralizing antibody titers could be boosted to very high levels 2-5 years following Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.
“Replicating Ad4 delivered to the URT causes prolonged exposure to antigen, drives durable systemic and mucosal immunity, and is a promising platform for the induction of immunity against viral surface glycoprotein targets,” the authors wrote.
The investigators said replication-competent vector vaccines are advantageous because they can express viral proteins at higher levels and for longer durations.
The researchers also said the vaccine platform could be adaptable for use against other viruses, such as HIV and SARS-CoV-2.
The study, “A replication competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity,” was published online in The Journal of Clinical Investigation.