Longevity of adenovirus vector immunity in mice and its implications for vaccine efficacy

Abstract

There is a high incidence of adenovirus (AdV) infection in humans due to the presence of more than 60 types of human adenoviruses (HAdVs). The majority of individuals are exposed to one or more HAdV types early in their lives, leading to the development of AdV type-specific neutralizing antibodies. Similarly, immunization or gene therapy with AdV vectors leads to immune responses to the AdV vector. This ‘vector immunity’ is a concern for AdV vector-based applications for vaccines or gene therapy, especially when the repeated administration of a vector is required. The objective of this investigation was to establish whether AdV neutralizing antibody titers decline sufficiently in a year to permit annual vaccination with the same AdV vector. Naïve or human adenoviral vector group C, serotype 5 (HAdV-C5)-primed mice were mock-inoculated (with PBS) or inoculated i.m. with 108 PFU of either HAd-GFP [HAdV-C5 vector expressing the green fluorescent protein (GFP)] to mimic the conditions for the first inoculation with an AdV vector-based vaccine. At 1, 3, 6, and 10 months post-HAd-GFP inoculation, naïve- or HAdV-primed animals were vaccinated i.m. with 108 PFU of HAd-H5HA [HAdV-C5 vector expressing hemagglutinin (HA) of H5N1 influenza virus]. There was a significant continual decrease in vector immunity titers with time, thereby leading to significant continual increases in the levels of HA-specific humoral and cell-mediated immune responses. In addition, significant improvement in protection efficacy against challenge with an antigenically heterologous H5N1 virus was observed in HAdV-primed animals at 6 months and onwards. These results indicate that the annual immunization with the same AdV vector may be effective due to a significant decline in vector immunity.

Nonhuman Adenoviral Vector-Based Platforms and Their Utility in Designing Next Generation of Vaccines for Infectious Diseases

“…The longevity of vector-specific neutralizing antibodies in people vaccinated with an Ad vector-based COVID-19 vaccine will determine whether annual immunization with the same Ad vector will be feasible without impacting the quality of protective immune responses. Our study to determine the longevity of vector immunity and its impact on the resultant antigen-specific immunity in mice implies that yearly vaccination with the same vector may be possible [ 137 ]. If an acceptable decline in vector-specific neutralizing antibodies within a year is not achieved, we will be better off using a different Ad vector-based vaccine for effective protection.…”

Adenoviral Vectors as Vaccines for Emerging Avian Influenza Viruses

“…However, in our opinion, the use of an alternative Ad serotype such as the Ad26 or ChAdOx1 vector, or a completely different vaccine platform as a booster would be preferable in eliciting an optimal immune response. Alternatively, increasing the interval between re-administration of the same Ad vector, or altering the route of administration may help to overcome the effects of anti-vector immunity, as demonstrated in mice ( 232 , 243 , 244 ).…”

Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines

“…with 10 8 plaque-forming units (PFU) of HAd-H5HA (HAd5 vector expressing H5N1 HA) at 1, 3, 6, and 10 months post HAd priming [ 52 ]. With time, there was a continual decline in HAd5 vector neutralization antibody titers with constant rises in the levels of HA-specific humoral and CMI responses, resulting in significant protection against challenge with an antigenically distinct H5N1 influenza virus at 6 months and onward [ 52 ]. These findings suggest that yearly immunization with the same vector is possible due to a significant drop in the vector immunity.…”

“…Due to the high seroprevalence of HAd5 in humans [ 24 , 41 , 44 , 48 , 53 ], which affects the potency of HAd5 vectored vaccines [ 46 , 52 , 54 ], rare human Ads such as HAd6, HAd11, HAd19a, HAd26, HAd28, HAd35, HAd48, and HAd49 [ 43 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] were developed as vectors for vaccine and gene therapy to circumvent the preexisting vector immunity. In addition, nonhuman Ad vectors (bovine Ad (BAd), chimpanzee Ad (chAd), porcine Ad (PAd), Canine Ad (CAd), and others) [ 47 , 53 , 62 , 63 , 64 ] demonstrated significant potential to overcome the preexisting vector immunity.…”