The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥ 1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine.

Measles is a highly contagious disease that most commonly strikes children. The causative agent, measles virus (MV), is generally transmitted by aerosolized secretions deposited on upper-respiratory-tract mucosal surfaces. Exposure leads to local respiratory tract replication; infection of regional lymphoid tissues then occurs followed by viremia and systemic dissemination as revealed by the characteristic skin rash. Most children recover uneventfully from the illness, but serious complications can occur, including pneumonia and involvement of the central nervous system (17,27,28). Despite the highly contagious nature of the disease, MV can be controlled effectively by immunization with live attenuated vaccines. The effectiveness of MV vaccines is well illustrated by the epidemiology of the disease in the United States. Prior to 1963, before use of the earliest vaccines, there were over 500,000 reported cases per year. Twenty years later, MV incidence was less than 2,000 cases per year (11,28). The availability of these effective vaccines has not eliminated the threat from MV, and measles still causes significant levels of morbidity and mortality in developing countries largely because of inadequate and unsustained vaccination efforts (17).Several effective MV vaccines were derived from a single clinical viral isolate called the Edmonston strain (28, 66). Enders et al. (20) developed the first MV vaccine by the classical approach (1) of propagating the pathogen in heterologous cells and tissues. Specifically, MV was serially propagated in semipermissive chicken embryos and chick fibroblast cells. Variations of the Enders approach have led to the development of a number of independently derived but effective Edmonstonbased vaccines (28,66).MV is a member of the genus Morbillivirus in the Paramyxoviridae family and, like other members of this family, it is an enveloped RNA virus that contains a single-strand, negativesense, nonsegmented genome (28, 47). The 16-kb MV genome encodes eight known proteins from six nonoverlapping cistrons arranged 3Ј-N-P-M-F-H-L-5Ј. The major structural polypeptide is encoded by the N (nucleocapsid) gene. The N protein is essential for packaging the genome into a ribonucleoprotein complex that serves as template for transcription, replication, and packaging into progeny virions. The P cistron specifies three polypeptides: P, C, and V. The P (phosphoprotein) polypeptide is a subunit of the viral RNA polymerase. P protein also acts as a chaperone that interacts with and regulates the cellular localization of N protein and probably assists in nucleocapsid assembly (28,33,70). The C and V polypeptides are nonstructural proteins that are translated from P mRNAs through the use of alternative reading frames; C protein is synthesized from a downstream translation start signal, whereas V protein is translated from an edited mRNA that contains an extra G residue (28,33,70). The M gene encodes the matrix protein that lines the inner surface of the viral envelope and participates in virion matur...

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The noncoding sequence of five Edmonston vaccine viruses (AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb) and those of a low-passage Edmonston wild-type (wt) measles virus have been determined and compared. Twenty-one nucleotide positions were identified at which Edmonston wt and one or more vaccine strains differed. The location of some of these nucleotide substitutions suggests that they may influence the efficiency of mRNA synthesis, processing, and translation, as well as genome replication and encapsidation. Five nucleotide substitutions were conserved in all of the vaccine strains. Two of these were in the genomic 3-terminal transcriptional control region and could affect RNA synthesis or encapsidation. Three were found within the 5-untranslated region of the F mRNA, potentially altering translation control sequences. The remaining vaccine virus base changes were found in one to four vaccine strains. Their genomic localization suggests that some may modify cis-acting regulatory domains, including the Kozak consensus element of the P and M genes, the F gene-end signal, and the F mRNA 5-untranslated sequence.

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