Neal A. Halsey

Expert Review on Poliovirus Immunity and Transmission

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

Review and Assessment of Poliovirus Immunity and Transmission: Synthesis of Knowledge Gaps and Identification of Research Needs

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.

Rationale for the Development of a Rotavirus Vaccine for Infants and Young Children

Vaccinology is a relatively new term, but its very existence reflects the progress in vaccine development. The field of vaccinology embraces the breadth of biology ranging from molecular biologic initiatives to conven-tional, well-established techniques.

Maternal IgG1 and IgA antibody to V3 loop consensus sequence and maternal-infant HIV-1 transmission

MatemaI lgG1 aod IgA antibody to V3 loop coosensus seqwnce and matemaI-infant HIV-1 trtmsmissioa Markham R.B.; Coberly J.; Ruff A.J.; Hoover D.; Gomez J.; Holt E.; Desormeaux J.; Boulos R.; Quinn T.C.; Halsey N.A. USA LANCET 1994 343/8894 (390-391) Maternal-infant transmission of HIV-I occurs in l3-40% of pregnancies. Studies of transmission of maternal immunity to HIV antigens have used antigens from viruses not represented of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgGl antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (P = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.

Early diagnosis of perinatal HIV infection by detection of viral specific IgA antibodies

Early tllqpds of perinatal HIV infection by detection of viralspecifk IgA antibodi~ Quinn TC,‘Kline RL, Halsey N; Hutton N; RutT A; Butz A; Boulos R; Modlin JF Blalock 1111, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21205, USA J AM MED ASSOC 1991 266124 (3439-3442) Objectives To evaluate the clinical utility of a human immunodeficiency virus (HIV)&4 serological assay for diagnosis of perinatahy acquired HIV infection. Design Coded serum samples prospectively collected from children born to HIVinfected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. Setting A university hospital in Baltimore, MD and an outpatient clinic in Port-au-Prince, Haiti. Population Five hundmd thirty-nine serum samples were obtained sequentially from 278 children born to HIVinfected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. Outcome Measures Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity and predictive values were calculated at different ages and collectively for children 3 months of age or older. Results The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7% and the positive and negative predictive values were 99.4% and 98.7%, respectively. Conclusion Although the HIV-@4 assay had a low sensitivity within the first months of life, the high sensitivity, specificity and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries.