A multifaceted approach to RSV vaccination

Abstract

Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur throughout different ages, thus, maintaining the virus in circulation, and increasing health risk to more susceptible populations such as infants, the elderly, and the immunocompromised. To date, there is no vaccine approved to prevent RSV infection or minimize symptoms of infection. Current clinical trials for vaccines against RSV are being carried out in four very different populations. There are vaccines that target two different pediatric populations, infants 2 to 6 month of age and seropositive children over 6 months of age, as well as women (non-pregnant or pregnant in their third trimester). There are vaccines that target adult and elderly populations. In this review, we will present and discuss RSV vaccine candidates currently in clinical trials. We will describe the preclinical studies instrumental for their advancement, with the goal of introducing new preclinical models that may more accurately predict the outcome of clinical vaccine studies.

Keywords: Cotton rat; RSV; maternal immunization; pregnancy.

Figure 1.

RSV vaccination of animals with passively transferred maternal RSV immunity. (A) Diagram of the experiment. Female cotton rats were primed by infection with RSV A/Long (10⁵ pfu i.n.) or left unprimed. All females were set in breeding pairs 5 weeks after RSV infection, and on week 9, females began delivering pups. At 4 weeks of age, pups were vaccinated with live RSV i.m., or left unvaccinated (-). Four weeks later, serum was collected from each pup and animals were challenged with RSV i.n. Four days after infection, pups were euthanized for determination of lung and nose viral titers. (B) NA titers of 4-week old pups born to unprimed or primed mothers. Insert shows mothers' NA titers in sera collected before delivery, indicating that all primed mothers produced NA. (C) NA titers in sera obtained from pups born to naïve or RSV-primed mothers after i.m. vaccination with live RSV (samples collected at week 8 prior to RSV challenge). (D) Lung and nose viral titers measured in samples obtained from pups born to naïve or RSV-primed mothers after vaccination of pups with PBS (-), or live RSV i.m. All animals were challenged i.n. with RSV/A Long (10⁵ pfu) and euthanized 4 days later. ANOVA followed by Student-Newman-Keuls post hoc test. *p<0.01. Data taken from reference.

Figure 2.

Efficiency of protection against RSV in juvenile cotton rats born from vaccinated, unprimed or primed mothers. (A) Female cotton rats were separated into three groups. One group of females remained unprimed and unvaccinated (Group A) as a control. Another group was primed by infection with RSV i.n. and then vaccinated with live RSV i.m. two weeks after priming and boosted during pregnancy (Group B). The last group of females remained unprimed, but was vaccinated and boosted (Group C). Litters from mothers in each group were challenged 4 weeks after birth and euthanized on day 4 post-challenge. (B) Quantification of lung and nose viral titers in samples of RSV-challenged, 4-week old juvenile cotton rats. Bars represent the mean ± SE. The inhibitory effect on vaccination in seropositive mothers was evaluated by comparing litters born from mothers in Group B (primed) and Group C (unprimed). N = 13-25 pups per group. ANOVA followed by Student-Newman-Keuls post hoc test. *p < 0.01. Data taken from reference.