Fred M. Davenport

Hybrid Formation of Influenza Virus at 25

Summary It is clear that “cold hybrids” of influenza virus can be obtained at 25° by recombination of two live influenza virus, of human and animal origins, one of which is cold-adapted. The presently described “cold hybrids” contain the hemagglutinin of the current human or equine strains and the neuraminidase of the established “cold variant”. These derived lines can grow at 25° in tissue culture and embryonated eggs and are also able to form plaques at 25°. They can grow in mouse lungs and are temperature sensitive. The Hong Kong “cold hybrid” (CHI) is attenuated for animals and highly immunogenic. Since only about four weeks were required to obtain these strains, it is evident that the procedures used offer potential practical advantages for production of live influenza vaccine strains. The authors wish to acknowledge the technical assistance of Mrs. Jeanne Thompson.

Applied immunology of mineral oil adjuvants

I N 1956, in reviewing the historical development of the use of water-in-oil emulsions as immunologic adjuvants, Jules Freund wrote the following succinct statement. “The past of the whole subject is long, but its history is rather short. Indeed in retrospect one wonders at the disproportion between the length of time and the fewness of the steps that separate the basic observations from their successful application.“l In the preceding year, Dr. Freund addressed the American Academy of Allergy at its Eleventh Annual Meeting and one of his characteristically cautious conclusions was, “The use of adjuvants may find application in prophylactic immunization and preseasonal treatment of allergic patients.“2 Jules Freund was responsible for many of the steps which made it possible to bridge the gaps between the basic observations and their application.” Today, therefore, in recognition of the central role he played in the development of mineral oil adjuvants, it seems appropriate to recount before this society some of these basic observations and to interpret their significance, since, by now, the unique advantages of mineral oil adjuvants have been utilized successfully for prophylactic immunization of man and for the treatment of allergic patients.

Antigenic Enhancement of Ether-Extracted Influenza Virus Vaccines by AlPO4

Summary Virus vaccines with AlPO4, HA vaccines and HA vaccines with AlPO4 were prepared as monovalent suspensions using 4 strains of influenza A and 2 of influenza B. In all cases, dilutions of the HA vaccines induced lower antibody levels and lower levels of immunity than their virus counterparts. Addition of AlPO4 restored the antigenicity of HA vaccines to levels almost equal to those of whole virus vaccines. The significance of these findings is briefly discussed.

The clinical epidemiology of Asian influenza.

Excerpt In February, 1957, viruses belonging to a previously unrecognized family of influenza A strains emerged from North China and within four months were disseminated throughout the globe.1, 2Th...

New Research on Influenza: Studies with Normal Volunteers: Combined Clinical Staff Conference at the National Institutes of Health

Excerpt Dr. Vernon Knight: Todays conference will consist of a description of three investigations of influenza in normal volunteers at the Clinical Center, National Institutes of Health. Dr. Juli...

Studies on Vaccination of Infants Against Influenza with Influenza Hemagglutinin

Summary Infants 2-6 mo of age were given 3 doses of influenza hemagglutinin vaccine. One group received 250 CCA units of vaccine at intervals of 1 mo. A second group was given 250 CCA units with an interval of 2 mo between the first and second dose and an interval of 1 mo between the second and third dose. A slightly better antibody response was obtained with this schedule. In a second experiment, infants 6-9 mo of age were given an initial series of either 300 CCA units of aqueous or aluminum phosphate adsorbed hemagglutinin vaccine. These infants exhibited a better antibody response than younger ones. When after 9-12 mo a third dose of the same vaccine was given, a secondary response was achieved. The response of infants who received adsorbed vaccine was slightly higher. The response of infants to polyvalent influenza hemagglutinin is similar to their response to other inactivated vaccines.

Reflections on the epidemiology of myxovirus infections.

In the last few years there has been an explosive increase in our knowledge of the molecular biology of myxoviruses. Some of this information has been used to formulate new hypotheses concerning the epidemiology of myxovirus infections. For acceptance, epidemiologic hypotheses, like others, must provide satisfactory explanations for all of the known findings not for just a convenient subset of them. The following mysteries present formidable challenges to current formulations.

Antibody Response to Influenza Virus Enzyme in Man

Antineuraminidase antibody levels were mea.. sured by inhibition of hemagglutination employing recombinant strain X-15 in paired sera of human subjects naturally infected with influenza AO, and A2, strains and in sets of sera obtained from persons vaccinated with swine, AO, A1, or A2 monovalent vaccines. The antineuraminidase antibody increase found with the X-15 test after infection and vaccination was shown to be subtype specific for A2 enzymes. The frequency and mag.. nitude antibody increase after both types of antigenic experience was similar. An ether-extracted hemagglutinin vaccine was, as efficient as its whole virus counterpart in stimulating antienzyme antibodies. Reinforcement of antienzyme antibody levels and antigenic broadening of the antibody response on repeated exposures was demonstrated.

An imporved procedure for measuring neuraminidase antibodies by hemagglutination-inhibition.

Neuraminidase antibodies are known to inhibit hemagglutination by X-15 and X-15 (HK) recombinant viruses. However, the level of inhibition observed varies when different batches of chicken erythrocytes are employed, and the test generally detects neuraminidase antibodies with less sensitivity than an enzyme inhibition test. By titrating neuraminidase antibodies in the presence of anti-IgG globulins, with appropriate specificity, the hemagglutination-inhibition activity of neuraminidase antibodies is enhanced and the effect of cell variation is minimized. Consequently results obtained with this modified method for titrating neuraminidase antibodies become comparable to those obtained by measuring enzyme-inhibition. The improved hemagglutination-inhibition procedure possesses the important advantages of greater convenience and economy. Similar enhancing effects may also be obtained with egg white and guinea pig serum.

Clinical reactivity and immuno-genicity of hemagglutinin influenza vaccine. II. Clinical reactions, hemagglutination-inhibiting and strain and type-specific complement-fixing antibody responses in infants.

The reactivity and immunogenicity of a polyvalent hemagglutinin influenza vaccine was studied in subjects aged 5–7 months. The vaccine was administered in three doses either subcutaneously (0.5 ml per dose) or intradermally (0.1 ml per dose) over a period of 6–7 months. Clinical reactions, both local and febrile, even after administering two or three doses, were quite mild. After two 0.5 ml doses of vaccine administered subcutaneously, most subjects possessed hemagglutination-inhibition (HI) antibodies to all the six vaccine viruses. In most subjects the antibodies dropped to und etectable levels in the course of four to five months. A booster effect was observed after the third vaccine dose. Intradermal administration of the vaccine (0.1 ml) was much less efficient. Even three doses of vaccine did not induce antibody development in most subjects. The antibody response in the complement-fixation (CF) test using strain-specific V antigens corresponded, in general, with the results of the HI test; however the CF antibodies to the A 2/Taiwan and B/Md viruses were found much less frequently than the corresponding HI antibody. Most of the infants vaccinated subcutaneously also developed antibodies reactive in the CF test with the soluble (S) antigens of influenza A and B. They were much less frequent in subjects immunized intradermally.