Challenges for the Newborn Following Influenza Virus Infection and Prospects for an Effective Vaccine

Abstract

Newborns are at significantly increased risk of severe disease following infection with influenza virus. This is the collective result of their naïve status, altered immune responsiveness, and the lack of a vaccine that is effective in these individuals. Numerous studies have revealed impairments in both the innate and adaptive arms of the immune system of newborns. The consequence of these alterations is a quantitative and qualitative decrease in both antibody and T cell responses. This review summarizes the hurdles newborns experience in mounting an effective response that can clear influenza virus and limit disease following infection. In addition, the challenges, as well as the opportunities, for developing vaccines that can elicit protective responses in these at risk individuals are discussed.

Keywords: adjuvant; antibody; influenza; newborn; vaccine.

Figure 1

Reported and potential alterations in the newborn immune response following influenza virus infection. Newborns encounter challenges at multiple steps in the generation of an effective immune response following influenza virus infection. A number of these have been experimentally demonstrated in newborn animal models. These are indicated in black font. There are also alterations that seem highly likely in the context of influenza virus infection based on in vitro studies or other models of newborn responses as described in the text. However, they have not been directly shown for influenza virus infection of newborns. These proposed alterations are shown in red font.

Figure 2

Adjuvants and pathways reported to promote responses in newborns. A number of experimental adjuvants have been tested in the context of neonates or neonate derived cells. Some of these adjuvants impact multiple cell types, while others are more targeted. The results from these analyses suggest combinations of adjuvants may be needed to overcome the multiple impairments in the newborn immune response. A summary of a representative selection of promising adjuvants for newborns is shown. LN, lymph node; GC, germinal center; PC, plasma cell; Bmem, memory B cell; DC, dendritic cell; FDC, follicular dendritic cell.

Figure 3

Universal influenza vaccines as a first antigen exposure in newborns. Current influenza vaccine efforts are focused on the development of approaches that can provide broad strain recognition, i.e., a universal vaccine. These vaccines often target the conserved stem region of the HA molecule. The ability to successfully employ a universal vaccine that can work in newborns through appropriate adjuvantation would likely result in HA stem as the first influenza antigen exposure. Subsequent virus challenge should preferentially drive these universal specificities and may result in their higher representation compared to what would occur in individuals who received the stem vaccine later in life. Whether this single specificity response, e.g., stem-specific antibody, will provide adequate protection will need to be carefully assessed. QIIV, quadrivalent inactivated influenza vaccine.